Microfluidic Isolation of Circulating Tumor Cell Clusters by Size and Asymmetry

Abstract Circulating tumor cell clusters (CTC clusters) are potent initiators of metastasis and potentially useful clinical markers for patients with cancer. Although there are numerous devices developed to isolate individual circulating tumor cells from blood, these devices are ineffective at captu...

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Autores principales:	Sam H. Au, Jon Edd, Amy E. Stoddard, Keith H. K. Wong, Fabio Fachin, Shyamala Maheswaran, Daniel A. Haber, Shannon L. Stott, Ravi Kapur, Mehmet Toner
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0d495c2a2b8a41feaa99b11421967de5
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spelling	oai:doaj.org-article:0d495c2a2b8a41feaa99b11421967de52021-12-02T12:32:29ZMicrofluidic Isolation of Circulating Tumor Cell Clusters by Size and Asymmetry10.1038/s41598-017-01150-32045-2322https://doaj.org/article/0d495c2a2b8a41feaa99b11421967de52017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01150-3https://doaj.org/toc/2045-2322Abstract Circulating tumor cell clusters (CTC clusters) are potent initiators of metastasis and potentially useful clinical markers for patients with cancer. Although there are numerous devices developed to isolate individual circulating tumor cells from blood, these devices are ineffective at capturing CTC clusters, incapable of separating clusters from single cells and/or cause cluster damage or dissociation during processing. The only device currently able to specifically isolate CTC clusters from single CTCs and blood cells relies on the batch immobilization of clusters onto micropillars which necessitates long residence times and causes damage to clusters during release. Here, we present a two-stage continuous microfluidic chip that isolates and recovers viable CTC clusters from blood. This approach uses deterministic lateral displacement to sort clusters by capitalizing on two geometric properties: size and asymmetry. Cultured breast cancer CTC clusters containing between 2–100 + cells were recovered from whole blood using this integrated two-stage device with minimal cluster dissociation, 99% recovery of large clusters, cell viabilities over 87% and greater than five-log depletion of red blood cells. This continuous-flow cluster chip will enable further studies examining CTC clusters in research and clinical applications.Sam H. AuJon EddAmy E. StoddardKeith H. K. WongFabio FachinShyamala MaheswaranDaniel A. HaberShannon L. StottRavi KapurMehmet TonerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sam H. Au Jon Edd Amy E. Stoddard Keith H. K. Wong Fabio Fachin Shyamala Maheswaran Daniel A. Haber Shannon L. Stott Ravi Kapur Mehmet Toner Microfluidic Isolation of Circulating Tumor Cell Clusters by Size and Asymmetry
description	Abstract Circulating tumor cell clusters (CTC clusters) are potent initiators of metastasis and potentially useful clinical markers for patients with cancer. Although there are numerous devices developed to isolate individual circulating tumor cells from blood, these devices are ineffective at capturing CTC clusters, incapable of separating clusters from single cells and/or cause cluster damage or dissociation during processing. The only device currently able to specifically isolate CTC clusters from single CTCs and blood cells relies on the batch immobilization of clusters onto micropillars which necessitates long residence times and causes damage to clusters during release. Here, we present a two-stage continuous microfluidic chip that isolates and recovers viable CTC clusters from blood. This approach uses deterministic lateral displacement to sort clusters by capitalizing on two geometric properties: size and asymmetry. Cultured breast cancer CTC clusters containing between 2–100 + cells were recovered from whole blood using this integrated two-stage device with minimal cluster dissociation, 99% recovery of large clusters, cell viabilities over 87% and greater than five-log depletion of red blood cells. This continuous-flow cluster chip will enable further studies examining CTC clusters in research and clinical applications.
format	article
author	Sam H. Au Jon Edd Amy E. Stoddard Keith H. K. Wong Fabio Fachin Shyamala Maheswaran Daniel A. Haber Shannon L. Stott Ravi Kapur Mehmet Toner
author_facet	Sam H. Au Jon Edd Amy E. Stoddard Keith H. K. Wong Fabio Fachin Shyamala Maheswaran Daniel A. Haber Shannon L. Stott Ravi Kapur Mehmet Toner
author_sort	Sam H. Au
title	Microfluidic Isolation of Circulating Tumor Cell Clusters by Size and Asymmetry
title_short	Microfluidic Isolation of Circulating Tumor Cell Clusters by Size and Asymmetry
title_full	Microfluidic Isolation of Circulating Tumor Cell Clusters by Size and Asymmetry
title_fullStr	Microfluidic Isolation of Circulating Tumor Cell Clusters by Size and Asymmetry
title_full_unstemmed	Microfluidic Isolation of Circulating Tumor Cell Clusters by Size and Asymmetry
title_sort	microfluidic isolation of circulating tumor cell clusters by size and asymmetry
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/0d495c2a2b8a41feaa99b11421967de5
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Microfluidic Isolation of Circulating Tumor Cell Clusters by Size and Asymmetry

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