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However, such methods will not recover the fraction of CTCs that have a non-epithelial phenotype due to epithelial\u2013mesenchymal transition. For phenotype-independent CTC enrichment, we developed a new enhanced negative depletion strategy\u2014termed MINDEC\u2014that is based on multi-marker (CD45, CD16, CD19, CD163 and CD235a\/GYPA) depletion of blood cells rather than targeted enrichment of CTCs. Here we validated the performance of MINDEC using epithelial and mesenchymal cancer cell lines, demonstrating a mean recovery of 82\u2009\u00b1\u200910%, high depletion (437\u2009\u00b1\u2009350 residual white blood cells (WBCs)\/mL peripheral blood), linearity between spiked and recovered cells (correlation coefficient: <jats:italic>r<\/jats:italic>\u2009=\u20090.995) and a low detection limit (\u22651 cell recovered in all four replicates spiked with 3 cells). For clinical validation of this method, we enumerated CTCs in peripheral blood samples from patients with metastatic pancreatic cancer, detecting CTCs in 15 of 21 blood samples (71%) from 9 patients. The promising performance of the MINDEC enrichment strategy in our study encourages validation in larger clinical trials.<\/jats:p>","DOI":"10.1038\/srep28929","type":"journal-article","created":{"date-parts":[[2016,7,19]],"date-time":"2016-07-19T09:14:17Z","timestamp":1468919657000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["MINDEC-An Enhanced Negative Depletion Strategy for Circulating Tumour Cell Enrichment"],"prefix":"10.1038","volume":"6","author":[{"given":"Morten","family":"Lapin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kjersti","family":"Tjensvoll","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satu","family":"Oltedal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tove","family":"Buhl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bj\u00f8rnar","family":"Gilje","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rune","family":"Smaaland","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oddmund","family":"Nordg\u00e5rd","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,7,19]]},"reference":[{"key":"BFsrep28929_CR1","first-page":"146","volume":"14","author":"T Ashworth","year":"1869","unstructured":"Ashworth, T. 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