Inertial Focusing for Tumor Antigen–Dependent and –Independent Sorting of Rare Circulating Tumor Cells
Emre Ozkumur,Ajay Shah,Jordan C. Ciciliano,Benjamin L. Emmink,David T. Miyamoto,Elena F. Brachtel,Min Yu,Min Yu,Pin-i Chen,Bailey Morgan,Julie Trautwein,Anya Kimura,Sudarshana Sengupta,Shannon L. Stott,Nezihi Murat Karabacak,Tom Barber,John R. Walsh,Kyle C. Smith,Philipp S. Spuhler,James P. Sullivan,Richard T. Lee,David T. Ting,Xi Luo,Xi Luo,Alice T. Shaw,Aditya Bardia,Lecia V. Sequist,David N. Louis,Shyamala Maheswaran,Ravi Kapur,Daniel A. Haber,Daniel A. Haber,Mehmet Toner +32 more
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TLDR
A multistage microfluidic device that is capable of sorting rare circulating tumor cells (CTCs) that are either positive or negative for the surface antigen epithelial cell adhesion molecule (EpCAM) and could be a promising addition to current diagnostic tools used in the clinic is developed.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 107 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.read more
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Circulating Tumor Cell Clusters Are Oligoclonal Precursors of Breast Cancer Metastasis
Nicola Aceto,Aditya Bardia,David T. Miyamoto,Maria C. Donaldson,Ben S. Wittner,Joel A. Spencer,Min Yu,Adam Pely,Amanda Engstrom,Huili Zhu,Brian W. Brannigan,Ravi Kapur,Shannon L. Stott,Toshi Shioda,Sridhar Ramaswamy,David T. Ting,Charles P. Lin,Mehmet Toner,Daniel A. Haber,Daniel A. Haber,Shyamala Maheswaran +20 more
TL;DR: Using mouse models with tagged mammary tumors, it is demonstrated that CTC clusters arise from oligoclonal tumor cell groupings and not from intravascular aggregation events, and though rare in the circulation, they greatly contribute to the metastatic spread of cancer.
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Challenges in circulating tumour cell research.
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Microfluidic cell sorting: a review of the advances in the separation of cells from debulking to rare cell isolation
TL;DR: This review examines the breadth of microfluidic cell sorting technologies, while focusing on those that offer the greatest potential for translation into clinical and industrial practice and that offer multiple, useful functions.
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Ex vivo culture of circulating breast tumor cells for individualized testing of drug susceptibility
Min Yu,Min Yu,Aditya Bardia,Nicola Aceto,Francesca Bersani,Marissa W. Madden,Maria C. Donaldson,Rushil Desai,Huili Zhu,Valentine Comaills,Zongli Zheng,Zongli Zheng,Ben S. Wittner,Petar Stojanov,Elena F. Brachtel,Dennis C. Sgroi,Ravi Kapur,Toshihiro Shioda,David T. Ting,Sridhar Ramaswamy,Gad Getz,Gad Getz,A. John Iafrate,Cyril H. Benes,Mehmet Toner,Shyamala Maheswaran,Daniel A. Haber,Daniel A. Haber +27 more
TL;DR: It has been proposed that the isolation, ex vivo culture, and characterization of CTCs may provide an opportunity to noninvasively monitor the changing patterns of drug susceptibility in individual patients as their tumors acquire new mutations.
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Fundamentals and applications of inertial microfluidics: a review
Jun Zhang,Sheng Yan,Dan Yuan,Gursel Alici,Nam-Trung Nguyen,Majid Ebrahimi Warkiani,Weihua Li +6 more
TL;DR: This review discusses the fundamental kinematics of particles in microchannels to familiarise readers with the mechanisms and underlying physics in inertial microfluidic systems and presents a comprehensive review of recent developments and key applications of inertialMicrofluidics systems according to their microchannel structures.
References
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W. Jeffrey Allard,Jeri Matera,M. Craig Miller,Madeline Repollet,Mark Connelly,Chandra Rao,Arjan G.J. Tibbe,Jonathan W. Uhr,Leon W.M.M. Terstappen +8 more
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High gradient magnetic cell separation with MACS
TL;DR: A flexible, fast and simple magnetic cell sorting system for separation of large numbers of cells according to specific cell surface markers was developed and tested and makes this system an ideal complement to flow cytometry.
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