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To address these challenges, we developed IntravChip, a continuously perfused microfluidic platform containing a vascularized primary tumor microenvironment (TME) enabling the observation of TC intravasation, and a downstream chamber to collect intravasated TCs. The IntravChip can support a high TC concentration in the TME while maintaining complete vascular perfusion, which we found was necessary to collect intravasated cells. Using MDA-MB-231 breast TCs, we identified an optimal initial TC seeding density that, by day 9, yields a densely populated TME and 100-440 collected intravasated TCs. We validated the IntravChip across several TC types, showing that MDA-MB-231 and MV3 TCs have the highest intravasation rates while MCF-7 TCs have low intravasation efficiency. We also show that the IntravChip is compatible with super-resolution nano-imaging. Our devices enabled high-quality STochastic Optical Reconstruction Microscopy imaging, which revealed that H3K9me3 nanodomains are significantly differentially distributed in intravasated MDA-MB-231 TCs compared to those residing in the TME. Finally, the IntravChip was validated as a platform to test the effects of anti-cancer drugs on TCs and on the vasculature. We showed that a 5\n                    <jats:italic>\u03bc<\/jats:italic>\n                    M concentration of sorafenib reduced intravasation events by 69% without impacting the morphology of the microvascular networks, while a 10\n                    <jats:italic>\u03bc<\/jats:italic>\n                    M concentration led to a significant decrease in vessel diameter. This platform enables quantitative analysis of TC intravasation, collection of intravasated TCs for characterization, and screening of anti-metastatic therapies.\n                  <\/jats:p>","DOI":"10.1088\/1758-5090\/ae8721","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T22:50:57Z","timestamp":1783464657000},"page":"035033","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["IntravChip: a vascularized and perfused microfluidic model of the primary tumor microenvironment to collect intravasated tumor cells"],"prefix":"10.1088","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9027-7614","authenticated-orcid":true,"given":"Marie","family":"Floryan","sequence":"first","affiliation":[{"name":"Massachusetts Institute of Technology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2918-7131","authenticated-orcid":true,"given":"Alessandro","family":"Cordiale","sequence":"additional","affiliation":[{"name":"Information and Bioengineering, Politecnico di Milano"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather","family":"Jensen","sequence":"additional","affiliation":[{"name":"Massachusetts Institute of Technology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5984-6039","authenticated-orcid":true,"given":"Julie","family":"Chen","sequence":"additional","affiliation":[{"name":"Massachusetts Institute of Technology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0689-7096","authenticated-orcid":true,"given":"Zixian","family":"Guo","sequence":"additional","affiliation":[{"name":"University of Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinayak","family":"Vinayak","sequence":"additional","affiliation":[{"name":"University of Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9934-4297","authenticated-orcid":true,"given":"Sina","family":"Kheiri","sequence":"additional","affiliation":[{"name":"Massachusetts Institute of Technology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8657-9815","authenticated-orcid":true,"given":"Ritu","family":"Raman","sequence":"additional","affiliation":[{"name":"Massachusetts Institute of Technology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivek","family":"Shenoy","sequence":"additional","affiliation":[{"name":"University of Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6896-5421","authenticated-orcid":true,"given":"Elena","family":"Cambria","sequence":"additional","affiliation":[{"name":"Massachusetts Institute of Technology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7232-304X","authenticated-orcid":true,"given":"Roger","family":"Kamm","sequence":"additional","affiliation":[{"name":"Massachusetts Institute of Technology"},{"name":"Massachusetts Institute of Technology"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"266","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"bfae8721bib1","doi-asserted-by":"publisher","first-page":"4203","DOI":"10.1038\/onc.2013.377","type":"journal-article","article-title":"Macrophage contact induces RhoA GTPase signaling to trigger tumor cell intravasation","volume":"33","author":"Roh-johnson","year":"2014","journal-title":"Oncogene"},{"key":"bfae8721bib2","doi-asserted-by":"publisher","first-page":"932","DOI":"10.1158\/2159-8290.CD-15-0012","type":"journal-article","article-title":"Real-time imaging reveals local, transient vascular permeability, and tumor cell intravasation stimulated by TIE2hi macrophage\u2013derived VEGFA","volume":"5","author":"Harney","year":"2015","journal-title":"Cancer Discov."},{"key":"bfae8721bib3","first-page":"1627","type":"journal-article","article-title":"Tumor angiogenesis and its possible role in intravasation of colorectal epithelial cells","volume":"7","author":"Tien","year":"2001","journal-title":"Clin. 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