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As these applications are being translated to clinical use, processing larger volumes of blood in shorter timescales with high-reliability and robustness is becoming a pressing need. In this work, we report a scaled, label-free cell separation mechanism called non-equilibrium inertial separation array (NISA). The NISA mechanism consists of an array of islands that exert a passive inertial lift force on proximate cells, thus enabling gentler manipulation of the cells without the need of physical contact. As the cells follow their size-based, deterministic path to their equilibrium positions, a preset fraction of the flow is siphoned to separate the smaller cells from the main flow. The NISA device was used to fractionate 400\u2009mL of whole blood in less than 3\u2009hours, and produce an ultrapure buffy coat (96.6% white blood cell yield, 0.0059% red blood cell carryover) by processing whole blood at 3\u2009mL\/min, or \u223c300 million cells\/second. This device presents a feasible alternative for fractionating blood for transfusion, cellular therapy and blood-based diagnostics, and could significantly improve the sensitivity of rare cell isolation devices by increasing the processed whole blood volume.<\/jats:p>","DOI":"10.1038\/s41598-017-10295-0","type":"journal-article","created":{"date-parts":[[2017,8,24]],"date-time":"2017-08-24T07:45:34Z","timestamp":1503560734000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Non-equilibrium Inertial Separation Array for High-throughput, Large-volume Blood Fractionation"],"prefix":"10.1038","volume":"7","author":[{"given":"Baris R.","family":"Mutlu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle C.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon F.","family":"Edd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priyanka","family":"Nadar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mcolisi","family":"Dlamini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravi","family":"Kapur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehmet","family":"Toner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,8,30]]},"reference":[{"key":"10295_CR1","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1016\/j.blre.2012.01.003","volume":"26","author":"C Ganzel","year":"2012","unstructured":"Ganzel, C., Becker, J., Mintz, P. 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As a result of this license, M.T. and Massachusetts General Hospital (MGH) hold equity in MicroMedicine. No funding was received from MicroMedicine Inc. at the MGH for the reported studies.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"9915"}}