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Classification of large circulating tumor cells isolated with ultra-high throughput microfluidic Vortex technology

Circulating tumor cells (CTCs) are emerging as rare but clinically significant non-invasive cellular biomarkers for cancer patient prognosis, treatment selection, and treatment monitoring. Current CTC isolation approaches, such as immunoaffinity, filtration, or size-based techniques, are often limit...

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Autores principales: Che, James, Yu, Victor, Dhar, Manjima, Renier, Corinne, Matsumoto, Melissa, Heirich, Kyra, Garon, Edward B., Goldman, Jonathan, Rao, Jianyu, Sledge, George W., Pegram, Mark D., Sheth, Shruti, Jeffrey, Stefanie S., Kulkarni, Rajan P., Sollier, Elodie, Di Carlo, Dino
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4914319/
https://www.ncbi.nlm.nih.gov/pubmed/26863573
http://dx.doi.org/10.18632/oncotarget.7220
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author Che, James
Yu, Victor
Dhar, Manjima
Renier, Corinne
Matsumoto, Melissa
Heirich, Kyra
Garon, Edward B.
Goldman, Jonathan
Rao, Jianyu
Sledge, George W.
Pegram, Mark D.
Sheth, Shruti
Jeffrey, Stefanie S.
Kulkarni, Rajan P.
Sollier, Elodie
Di Carlo, Dino
author_facet Che, James
Yu, Victor
Dhar, Manjima
Renier, Corinne
Matsumoto, Melissa
Heirich, Kyra
Garon, Edward B.
Goldman, Jonathan
Rao, Jianyu
Sledge, George W.
Pegram, Mark D.
Sheth, Shruti
Jeffrey, Stefanie S.
Kulkarni, Rajan P.
Sollier, Elodie
Di Carlo, Dino
author_sort Che, James
collection PubMed
description Circulating tumor cells (CTCs) are emerging as rare but clinically significant non-invasive cellular biomarkers for cancer patient prognosis, treatment selection, and treatment monitoring. Current CTC isolation approaches, such as immunoaffinity, filtration, or size-based techniques, are often limited by throughput, purity, large output volumes, or inability to obtain viable cells for downstream analysis. For all technologies, traditional immunofluorescent staining alone has been employed to distinguish and confirm the presence of isolated CTCs among contaminating blood cells, although cells isolated by size may express vastly different phenotypes. Consequently, CTC definitions have been non-trivial, researcher-dependent, and evolving. Here we describe a complete set of objective criteria, leveraging well-established cytomorphological features of malignancy, by which we identify large CTCs. We apply the criteria to CTCs enriched from stage IV lung and breast cancer patient blood samples using the High Throughput Vortex Chip (Vortex HT), an improved microfluidic technology for the label-free, size-based enrichment and concentration of rare cells. We achieve improved capture efficiency (up to 83%), high speed of processing (8 mL/min of 10x diluted blood, or 800 μL/min of whole blood), and high purity (avg. background of 28.8±23.6 white blood cells per mL of whole blood). We show markedly improved performance of CTC capture (84% positive test rate) in comparison to previous Vortex designs and the current FDA-approved gold standard CellSearch assay. The results demonstrate the ability to quickly collect viable and pure populations of abnormal large circulating cells unbiased by molecular characteristics, which helps uncover further heterogeneity in these cells.
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spelling pubmed-49143192016-07-11 Classification of large circulating tumor cells isolated with ultra-high throughput microfluidic Vortex technology Che, James Yu, Victor Dhar, Manjima Renier, Corinne Matsumoto, Melissa Heirich, Kyra Garon, Edward B. Goldman, Jonathan Rao, Jianyu Sledge, George W. Pegram, Mark D. Sheth, Shruti Jeffrey, Stefanie S. Kulkarni, Rajan P. Sollier, Elodie Di Carlo, Dino Oncotarget Research Paper Circulating tumor cells (CTCs) are emerging as rare but clinically significant non-invasive cellular biomarkers for cancer patient prognosis, treatment selection, and treatment monitoring. Current CTC isolation approaches, such as immunoaffinity, filtration, or size-based techniques, are often limited by throughput, purity, large output volumes, or inability to obtain viable cells for downstream analysis. For all technologies, traditional immunofluorescent staining alone has been employed to distinguish and confirm the presence of isolated CTCs among contaminating blood cells, although cells isolated by size may express vastly different phenotypes. Consequently, CTC definitions have been non-trivial, researcher-dependent, and evolving. Here we describe a complete set of objective criteria, leveraging well-established cytomorphological features of malignancy, by which we identify large CTCs. We apply the criteria to CTCs enriched from stage IV lung and breast cancer patient blood samples using the High Throughput Vortex Chip (Vortex HT), an improved microfluidic technology for the label-free, size-based enrichment and concentration of rare cells. We achieve improved capture efficiency (up to 83%), high speed of processing (8 mL/min of 10x diluted blood, or 800 μL/min of whole blood), and high purity (avg. background of 28.8±23.6 white blood cells per mL of whole blood). We show markedly improved performance of CTC capture (84% positive test rate) in comparison to previous Vortex designs and the current FDA-approved gold standard CellSearch assay. The results demonstrate the ability to quickly collect viable and pure populations of abnormal large circulating cells unbiased by molecular characteristics, which helps uncover further heterogeneity in these cells. Impact Journals LLC 2016-02-06 /pmc/articles/PMC4914319/ /pubmed/26863573 http://dx.doi.org/10.18632/oncotarget.7220 Text en Copyright: © 2016 Che et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Che, James
Yu, Victor
Dhar, Manjima
Renier, Corinne
Matsumoto, Melissa
Heirich, Kyra
Garon, Edward B.
Goldman, Jonathan
Rao, Jianyu
Sledge, George W.
Pegram, Mark D.
Sheth, Shruti
Jeffrey, Stefanie S.
Kulkarni, Rajan P.
Sollier, Elodie
Di Carlo, Dino
Classification of large circulating tumor cells isolated with ultra-high throughput microfluidic Vortex technology
title Classification of large circulating tumor cells isolated with ultra-high throughput microfluidic Vortex technology
title_full Classification of large circulating tumor cells isolated with ultra-high throughput microfluidic Vortex technology
title_fullStr Classification of large circulating tumor cells isolated with ultra-high throughput microfluidic Vortex technology
title_full_unstemmed Classification of large circulating tumor cells isolated with ultra-high throughput microfluidic Vortex technology
title_short Classification of large circulating tumor cells isolated with ultra-high throughput microfluidic Vortex technology
title_sort classification of large circulating tumor cells isolated with ultra-high throughput microfluidic vortex technology
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4914319/
https://www.ncbi.nlm.nih.gov/pubmed/26863573
http://dx.doi.org/10.18632/oncotarget.7220
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