Monolithic Chip for High-throughput Blood Cell Depletion to Sort Rare Circulating Tumor Cells
Abstract Circulating tumor cells (CTCs) are a treasure trove of information regarding the location, type and stage of cancer and are being pursued as both a diagnostic target and a means of guiding personalized treatment. Most isolation technologies utilize properties of the CTCs themselves such as...
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2017
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oai:doaj.org-article:451a9d3337944460bed973cc5aa9b39f2021-12-02T15:05:46ZMonolithic Chip for High-throughput Blood Cell Depletion to Sort Rare Circulating Tumor Cells10.1038/s41598-017-11119-x2045-2322https://doaj.org/article/451a9d3337944460bed973cc5aa9b39f2017-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-11119-xhttps://doaj.org/toc/2045-2322Abstract Circulating tumor cells (CTCs) are a treasure trove of information regarding the location, type and stage of cancer and are being pursued as both a diagnostic target and a means of guiding personalized treatment. Most isolation technologies utilize properties of the CTCs themselves such as surface antigens (e.g., epithelial cell adhesion molecule or EpCAM) or size to separate them from blood cell populations. We present an automated monolithic chip with 128 multiplexed deterministic lateral displacement devices containing ~1.5 million microfabricated features (12 µm–50 µm) used to first deplete red blood cells and platelets. The outputs from these devices are serially integrated with an inertial focusing system to line up all nucleated cells for multi-stage magnetophoresis to remove magnetically-labeled white blood cells. The monolithic CTC-iChip enables debulking of blood samples at 15–20 million cells per second while yielding an output of highly purified CTCs. We quantified the size and EpCAM expression of over 2,500 CTCs from 38 patient samples obtained from breast, prostate, lung cancers, and melanoma. The results show significant heterogeneity between and within single patients. Unbiased, rapid, and automated isolation of CTCs using monolithic CTC-iChip will enable the detailed measurement of their physicochemical and biological properties and their role in metastasis.Fabio FachinPhilipp SpuhlerJoseph M. Martel-FoleyJon F. EddThomas A. BarberJohn WalshMurat KarabacakVincent PaiMelissa YuKyle SmithHenry HwangJennifer YangSahil ShahRuby YarmushLecia V. SequistShannon L. StottShyamala MaheswaranDaniel A. HaberRavi KapurMehmet TonerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017) |
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Medicine R Science Q Fabio Fachin Philipp Spuhler Joseph M. Martel-Foley Jon F. Edd Thomas A. Barber John Walsh Murat Karabacak Vincent Pai Melissa Yu Kyle Smith Henry Hwang Jennifer Yang Sahil Shah Ruby Yarmush Lecia V. Sequist Shannon L. Stott Shyamala Maheswaran Daniel A. Haber Ravi Kapur Mehmet Toner Monolithic Chip for High-throughput Blood Cell Depletion to Sort Rare Circulating Tumor Cells |
| description |
Abstract Circulating tumor cells (CTCs) are a treasure trove of information regarding the location, type and stage of cancer and are being pursued as both a diagnostic target and a means of guiding personalized treatment. Most isolation technologies utilize properties of the CTCs themselves such as surface antigens (e.g., epithelial cell adhesion molecule or EpCAM) or size to separate them from blood cell populations. We present an automated monolithic chip with 128 multiplexed deterministic lateral displacement devices containing ~1.5 million microfabricated features (12 µm–50 µm) used to first deplete red blood cells and platelets. The outputs from these devices are serially integrated with an inertial focusing system to line up all nucleated cells for multi-stage magnetophoresis to remove magnetically-labeled white blood cells. The monolithic CTC-iChip enables debulking of blood samples at 15–20 million cells per second while yielding an output of highly purified CTCs. We quantified the size and EpCAM expression of over 2,500 CTCs from 38 patient samples obtained from breast, prostate, lung cancers, and melanoma. The results show significant heterogeneity between and within single patients. Unbiased, rapid, and automated isolation of CTCs using monolithic CTC-iChip will enable the detailed measurement of their physicochemical and biological properties and their role in metastasis. |
| format |
article |
| author |
Fabio Fachin Philipp Spuhler Joseph M. Martel-Foley Jon F. Edd Thomas A. Barber John Walsh Murat Karabacak Vincent Pai Melissa Yu Kyle Smith Henry Hwang Jennifer Yang Sahil Shah Ruby Yarmush Lecia V. Sequist Shannon L. Stott Shyamala Maheswaran Daniel A. Haber Ravi Kapur Mehmet Toner |
| author_facet |
Fabio Fachin Philipp Spuhler Joseph M. Martel-Foley Jon F. Edd Thomas A. Barber John Walsh Murat Karabacak Vincent Pai Melissa Yu Kyle Smith Henry Hwang Jennifer Yang Sahil Shah Ruby Yarmush Lecia V. Sequist Shannon L. Stott Shyamala Maheswaran Daniel A. Haber Ravi Kapur Mehmet Toner |
| author_sort |
Fabio Fachin |
| title |
Monolithic Chip for High-throughput Blood Cell Depletion to Sort Rare Circulating Tumor Cells |
| title_short |
Monolithic Chip for High-throughput Blood Cell Depletion to Sort Rare Circulating Tumor Cells |
| title_full |
Monolithic Chip for High-throughput Blood Cell Depletion to Sort Rare Circulating Tumor Cells |
| title_fullStr |
Monolithic Chip for High-throughput Blood Cell Depletion to Sort Rare Circulating Tumor Cells |
| title_full_unstemmed |
Monolithic Chip for High-throughput Blood Cell Depletion to Sort Rare Circulating Tumor Cells |
| title_sort |
monolithic chip for high-throughput blood cell depletion to sort rare circulating tumor cells |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/451a9d3337944460bed973cc5aa9b39f |
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