A Size-Selective Intracellular Delivery Platform
Identifying and separating a subpopulation of cells from a heterogeneous mixture are essential elements of biological research. Current approaches require detailed knowledge of unique cell surface properties of the target cell population. A method is described that exploits size differences of cells...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Wiley Blackwell
2017
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| Online Access: | http://hdl.handle.net/1721.1/111674 https://orcid.org/0000-0001-9099-9281 https://orcid.org/0000-0003-4555-2485 https://orcid.org/0000-0002-1487-9568 https://orcid.org/0000-0003-4255-0492 https://orcid.org/0000-0001-7192-580X https://orcid.org/0000-0003-0921-3144 |
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| author | Patel, Nehal Mino-Kenudson, Mari Thayer, Sarah P. Liss, Andrew S. Saung, May Tun Sharei, Armon Reza Adalsteinsson, Viktor A. Cho, Nahyun Ruiz, Camilo A. Kirkpatrick, Jesse D. Langer, Robert S Jensen, Klavs F Love, John C Kamath, Tushar V. |
| author2 | Massachusetts Institute of Technology. Department of Chemical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Chemical Engineering Patel, Nehal Mino-Kenudson, Mari Thayer, Sarah P. Liss, Andrew S. Saung, May Tun Sharei, Armon Reza Adalsteinsson, Viktor A. Cho, Nahyun Ruiz, Camilo A. Kirkpatrick, Jesse D. Langer, Robert S Jensen, Klavs F Love, John C Kamath, Tushar V. |
| author_sort | Patel, Nehal |
| collection | MIT |
| description | Identifying and separating a subpopulation of cells from a heterogeneous mixture are essential elements of biological research. Current approaches require detailed knowledge of unique cell surface properties of the target cell population. A method is described that exploits size differences of cells to facilitate selective intracellular delivery using a high throughput microfluidic device. Cells traversing a constriction within this device undergo a transient disruption of the cell membrane that allows for cytoplasmic delivery of cargo. Unique constriction widths allow for optimization of delivery to cells of different sizes. For example, a 4 μm wide constriction is effective for delivery of cargo to primary human T-cells that have an average diameter of 6.7 μm. In contrast, a 6 or 7 μm wide constriction is best for large pancreatic cancer cell lines BxPc3 (10.8 μm) and PANC-1 (12.3 μm). These small differences in cell diameter are sufficient to allow for selective delivery of cargo to pancreatic cancer cells within a heterogeneous mixture containing T-cells. The application of this approach is demonstrated by selectively delivering dextran-conjugated fluorophores to circulating tumor cells in patient blood allowing for their subsequent isolation and genomic characterization. |
| first_indexed | 2024-09-23T17:12:08Z |
| format | Article |
| id | mit-1721.1/111674 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T17:12:08Z |
| publishDate | 2017 |
| publisher | Wiley Blackwell |
| record_format | dspace |
| spelling | mit-1721.1/1116742022-10-03T11:07:19Z A Size-Selective Intracellular Delivery Platform Patel, Nehal Mino-Kenudson, Mari Thayer, Sarah P. Liss, Andrew S. Saung, May Tun Sharei, Armon Reza Adalsteinsson, Viktor A. Cho, Nahyun Ruiz, Camilo A. Kirkpatrick, Jesse D. Langer, Robert S Jensen, Klavs F Love, John C Kamath, Tushar V. Massachusetts Institute of Technology. Department of Chemical Engineering Koch Institute for Integrative Cancer Research at MIT Love, Christopher J. Saung, May Tun Sharei, Armon Reza Adalsteinsson, Viktor A. Cho, Nahyun Kamath, Tushar Ruiz, Camilo A. Kirkpatrick, Jesse D. Langer, Robert S Jensen, Klavs F Love, John C Identifying and separating a subpopulation of cells from a heterogeneous mixture are essential elements of biological research. Current approaches require detailed knowledge of unique cell surface properties of the target cell population. A method is described that exploits size differences of cells to facilitate selective intracellular delivery using a high throughput microfluidic device. Cells traversing a constriction within this device undergo a transient disruption of the cell membrane that allows for cytoplasmic delivery of cargo. Unique constriction widths allow for optimization of delivery to cells of different sizes. For example, a 4 μm wide constriction is effective for delivery of cargo to primary human T-cells that have an average diameter of 6.7 μm. In contrast, a 6 or 7 μm wide constriction is best for large pancreatic cancer cell lines BxPc3 (10.8 μm) and PANC-1 (12.3 μm). These small differences in cell diameter are sufficient to allow for selective delivery of cargo to pancreatic cancer cells within a heterogeneous mixture containing T-cells. The application of this approach is demonstrated by selectively delivering dextran-conjugated fluorophores to circulating tumor cells in patient blood allowing for their subsequent isolation and genomic characterization. National Institutes of Health (U.S.) (Grant R01GM101420-01A1) National Institutes of Health (U.S.) (Grant P01CA117969) National Cancer Institute (U.S.) (Grant P30-CA14051) 2017-10-02T18:34:58Z 2017-10-02T18:34:58Z 2016-11 2016-07 Article http://purl.org/eprint/type/JournalArticle 1613-6810 1613-6829 http://hdl.handle.net/1721.1/111674 Saung, May Tun et al. “A Size-Selective Intracellular Delivery Platform.” Small 12, 42 (September 2016): 5873–5881 © 2016 WILEY-VCH Verlag https://orcid.org/0000-0001-9099-9281 https://orcid.org/0000-0003-4555-2485 https://orcid.org/0000-0002-1487-9568 https://orcid.org/0000-0003-4255-0492 https://orcid.org/0000-0001-7192-580X https://orcid.org/0000-0003-0921-3144 en_US http://dx.doi.org/10.1002/smll.201601155 Small Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Wiley Blackwell Prof. Love via Erja Kajosalo |
| spellingShingle | Patel, Nehal Mino-Kenudson, Mari Thayer, Sarah P. Liss, Andrew S. Saung, May Tun Sharei, Armon Reza Adalsteinsson, Viktor A. Cho, Nahyun Ruiz, Camilo A. Kirkpatrick, Jesse D. Langer, Robert S Jensen, Klavs F Love, John C Kamath, Tushar V. A Size-Selective Intracellular Delivery Platform |
| title | A Size-Selective Intracellular Delivery Platform |
| title_full | A Size-Selective Intracellular Delivery Platform |
| title_fullStr | A Size-Selective Intracellular Delivery Platform |
| title_full_unstemmed | A Size-Selective Intracellular Delivery Platform |
| title_short | A Size-Selective Intracellular Delivery Platform |
| title_sort | size selective intracellular delivery platform |
| url | http://hdl.handle.net/1721.1/111674 https://orcid.org/0000-0001-9099-9281 https://orcid.org/0000-0003-4555-2485 https://orcid.org/0000-0002-1487-9568 https://orcid.org/0000-0003-4255-0492 https://orcid.org/0000-0001-7192-580X https://orcid.org/0000-0003-0921-3144 |
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