Microfluidic Isolation of Circulating Tumor Cell Clusters by Size and Asymmetry
File(s)
Published version
Author(s)
Type
Journal Article
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.
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.
Date Issued
2017-05-26
Date Acceptance
2017-03-27
Citation
Scientific Reports, 2017, 7
ISSN
2045-2322
Publisher
Nature Publishing Group
Journal / Book Title
Scientific Reports
Volume
7
Copyright Statement
This article is licensed under a Creative Commons Attribution 4.0 International
License, which permits use, sharing, adaptation, distribution and reproduction in any medium or
format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative
Commons license, and indicate if changes were made. The images or other third party material in this
article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the
material. If material is not included in the article’s Creative Commons license and your intended use is not permitted
by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the
copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
© The Author(s) 2017
License, which permits use, sharing, adaptation, distribution and reproduction in any medium or
format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative
Commons license, and indicate if changes were made. The images or other third party material in this
article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the
material. If material is not included in the article’s Creative Commons license and your intended use is not permitted
by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the
copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
© The Author(s) 2017
License URL
Subjects
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
DETERMINISTIC LATERAL DISPLACEMENT
PARTICLE SEPARATION
LUNG-CANCER
MICROEMBOLI
METASTASIS
Publication Status
Published
Article Number
2433