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Ultrahigh-throughput magnetic sorting of large blood volumes for epitope-agnostic isolation of circulating tumor cells.
Mishra, Avanish; Dubash, Taronish D; Edd, Jon F; Jewett, Michelle K; Garre, Suhaas G; Karabacak, Nezihi Murat; Rabe, Daniel C; Mutlu, Baris R; Walsh, John R; Kapur, Ravi; Stott, Shannon L; Maheswaran, Shyamala; Haber, Daniel A; Toner, Mehmet.
Afiliação
  • Mishra A; BioMEMS Resource Center, Charlestown, MA 02129.
  • Dubash TD; Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Boston, MA 02114.
  • Edd JF; Cancer Center, Massachusetts General Hospital, Boston, MA 02114.
  • Jewett MK; Harvard Medical School, Boston, MA 02115.
  • Garre SG; Cancer Center, Massachusetts General Hospital, Boston, MA 02114.
  • Karabacak NM; Harvard Medical School, Boston, MA 02115.
  • Rabe DC; BioMEMS Resource Center, Charlestown, MA 02129.
  • Mutlu BR; Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Boston, MA 02114.
  • Walsh JR; Cancer Center, Massachusetts General Hospital, Boston, MA 02114.
  • Kapur R; BioMEMS Resource Center, Charlestown, MA 02129.
  • Stott SL; Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Boston, MA 02114.
  • Maheswaran S; Cancer Center, Massachusetts General Hospital, Boston, MA 02114.
  • Haber DA; BioMEMS Resource Center, Charlestown, MA 02129.
  • Toner M; Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Boston, MA 02114.
Proc Natl Acad Sci U S A ; 117(29): 16839-16847, 2020 07 21.
Article em En | MEDLINE | ID: mdl-32641515
ABSTRACT
Circulating tumor cell (CTC)-based liquid biopsies provide unique opportunities for cancer diagnostics, treatment selection, and response monitoring, but even with advanced microfluidic technologies for rare cell detection the very low number of CTCs in standard 10-mL peripheral blood samples limits their clinical utility. Clinical leukapheresis can concentrate mononuclear cells from almost the entire blood volume, but such large numbers and concentrations of cells are incompatible with current rare cell enrichment technologies. Here, we describe an ultrahigh-throughput microfluidic chip, LPCTC-iChip, that rapidly sorts through an entire leukapheresis product of over 6 billion nucleated cells, increasing CTC isolation capacity by two orders of magnitude (86% recovery with 105 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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Separação Celular / Microfluídica / Ensaios de Triagem em Larga Escala / Células Neoplásicas Circulantes Limite: Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Separação Celular / Microfluídica / Ensaios de Triagem em Larga Escala / Células Neoplásicas Circulantes Limite: Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article