Ultrahigh-throughput magnetic sorting of large blood volumes for epitope-agnostic isolation of circulating tumor cells
Avanish Mishra, Taronish D. Dubash, Jon F., Michelle K. Jewett, Suhaas G. Garre, Murat Karabacak, Daniel C. Rabe, Baris R. Mutlu, John R. Walsh, Ravi Kapur, Shannon L. Stott, Shyamala Maheswaran, Daniel A. Haber, Mehmet Toner
Abstract
enrichment). Using soft iron-filled channels to act as magnetic microlenses, we intensify the field gradient within sorting channels. Increasing magnetic fields applied to inertially focused streams of cells effectively deplete massive numbers of magnetically labeled leukocytes within microfluidic channels. The negative depletion of antibody-tagged leukocytes enables isolation of potentially viable CTCs without bias for expression of specific tumor epitopes, making this platform applicable to all solid tumors. Thus, the initial enrichment by routine leukapheresis of mononuclear cells from very large blood volumes, followed by rapid flow, high-gradient magnetic sorting of untagged CTCs, provides a technology for noninvasive isolation of cancer cells in sufficient numbers for multiple clinical and experimental applications.