Inertial focusing for tumor antigen-dependent and -independent sorting of rare circulating tumor cells
Emre Ozkumur, Ajay M Shah, Jordan C Ciciliano, Benjamin L Emmink, David T Miyamoto, Elena Brachtel, Min Yu, Pin-i Chen, Bailey Morgan, Julie Trautwein, Anya Kimura, Sudarshana Sengupta, Shannon L Stott, Nezihi Murat Karabacak, Thomas A Barber, John R Walsh, Kyle Smith, Philipp S Spuhler, James P Sullivan, Richard J Lee, David T Ting, Xi Luo, Alice T Shaw, Aditya Bardia, Lecia V Sequist, David N Louis, Shyamala Maheswaran, Ravi Kapur, Daniel A Haber, Mehmet Toner, Emre Ozkumur, Ajay M Shah, Jordan C Ciciliano, Benjamin L Emmink, David T Miyamoto, Elena Brachtel, Min Yu, Pin-i Chen, Bailey Morgan, Julie Trautwein, Anya Kimura, Sudarshana Sengupta, Shannon L Stott, Nezihi Murat Karabacak, Thomas A Barber, John R Walsh, Kyle Smith, Philipp S Spuhler, James P Sullivan, Richard J Lee, David T Ting, Xi Luo, Alice T Shaw, Aditya Bardia, Lecia V Sequist, David N Louis, Shyamala Maheswaran, Ravi Kapur, Daniel A Haber, Mehmet Toner
Abstract
Circulating tumor cells (CTCs) are shed into the bloodstream from primary and metastatic tumor deposits. Their isolation and analysis hold great promise for the early detection of invasive cancer and the management of advanced disease, but technological hurdles have limited their broad clinical utility. We describe an inertial focusing-enhanced microfluidic CTC capture platform, termed "CTC-iChip," that is capable of sorting rare CTCs from whole blood at 10(7) cells/s. Most importantly, the iChip is capable of isolating CTCs using strategies that are either dependent or independent of tumor membrane epitopes, and thus applicable to virtually all cancers. We specifically demonstrate the use of the iChip in an expanded set of both epithelial and nonepithelial cancers including lung, prostate, pancreas, breast, and melanoma. The sorting of CTCs as unfixed cells in solution allows for the application of high-quality clinically standardized morphological and immunohistochemical analyses, as well as RNA-based single-cell molecular characterization. The combination of an unbiased, broadly applicable, high-throughput, and automatable rare cell sorting technology with generally accepted molecular assays and cytology standards will enable the integration of CTC-based diagnostics into the clinical management of cancer.
Conflict of interest statement
Competing interests: MGH filed for patent protection for the CTC-iChip technology. The authors declare that they have no competing interests.
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Source: PubMed