BioMEMS Resource Center, Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA
Avanish Mishra
BioMEMS Resource Center, Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Medical School, Boston, MA 02115, USA
Kyle C. Smith
BendBio, Inc., Sharon, MA 02067, USA
Ravi Kapur
BioMEMS Resource Center, Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; BendBio, Inc., Sharon, MA 02067, USA
Shyamala Maheswaran
Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Medical School, Boston, MA 02115, USA
Daniel A. Haber
Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Medical School, Boston, MA 02115, USA; Howard Hughes Medical Institute, Bethesda, MD 20815, USA
Mehmet Toner
BioMEMS Resource Center, Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Harvard Medical School, Boston, MA 02115, USA; Shriners Hospitals for Children, Boston, MA 02114, USA; Corresponding author
Summary: Circulating tumor cells (CTCs) enter the vasculature from solid tumors and disseminate widely to initiate metastases. Mining the metastatic-enriched molecular signatures of CTCs before, during, and after treatment holds unique potential in personalized oncology. Their extreme rarity, however, requires isolation from large blood volumes at high yield and purity, yet they overlap leukocytes in size and other biophysical properties. Additionally, many CTCs lack EpCAM that underlies much of affinity-based capture, complicating their separation from blood. Here, we provide a comprehensive introduction of CTC isolation technology, by analyzing key separation modes and integrated isolation strategies. Attention is focused on recent progress in microfluidics, where an accelerating evolution is occurring in high-throughput sorting of cells along multiple dimensions.
