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...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2017-05-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-01150-3 |
| _version_ | 1818425238836215808 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-14T14:10:46Z |
| format | Article |
| id | doaj.art-0d495c2a2b8a41feaa99b11421967de5 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-14T14:10:46Z |
| publishDate | 2017-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-0d495c2a2b8a41feaa99b11421967de52022-12-21T22:58:18ZengNature PortfolioScientific Reports2045-23222017-05-017111010.1038/s41598-017-01150-3Microfluidic Isolation of Circulating Tumor Cell Clusters by Size and AsymmetrySam H. Au0Jon Edd1Amy E. Stoddard2Keith H. K. Wong3Fabio Fachin4Shyamala Maheswaran5Daniel A. Haber6Shannon L. Stott7Ravi Kapur8Mehmet Toner9Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical SchoolCenter for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical SchoolCenter for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical SchoolCenter for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical SchoolCenter for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical SchoolDepartment of Surgery, Massachusetts General Hospital, Harvard Medical SchoolMassachusetts General Hospital Center for Cancer Research, Harvard Medical SchoolCenter for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical SchoolCenter for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical SchoolCenter for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical SchoolAbstract 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.https://doi.org/10.1038/s41598-017-01150-3 |
| spellingShingle | 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 Scientific Reports |
| title | 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_short | Microfluidic Isolation of Circulating Tumor Cell Clusters by Size and Asymmetry |
| title_sort | microfluidic isolation of circulating tumor cell clusters by size and asymmetry |
| url | https://doi.org/10.1038/s41598-017-01150-3 |
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