A vector-free microfluidic platform for intracellular delivery
Intracellular delivery of macromolecules is a challenge in research and therapeutic applications. Existing vector-based and physical methods have limitations, including their reliance on exogenous materials or electrical fields, which can lead to toxicity or off-target effects. We describe a microfl...
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| Format: | Article |
| Language: | en_US |
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National Academy of Sciences (U.S.)
2013
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| Online Access: | http://hdl.handle.net/1721.1/80382 https://orcid.org/0000-0001-5629-4798 https://orcid.org/0000-0001-7192-580X https://orcid.org/0000-0001-8046-2288 https://orcid.org/0000-0003-4255-0492 |
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| author | Sharei, Armon Reza Zoldan, Janeta Sim, Woo Young Cho, Nahyun Jackson, Emily L. Mao, Shirley Schneider, Sabine Kim, Kwang-Soo Han, Min-Joon Lytton-Jean, Abigail K. R. Basto, Pamela Antonia Jhunjhunwala, Siddharth Heller, Daniel A. Kang, Jeon Woong Hartoularos, George C. Anderson, Daniel Griffith Langer, Robert Jensen, Klavs F. Adamo, Andrea, 1975- Lee, Jungmin, Ph. D. Massachusetts Institute of Technology |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology Sharei, Armon Reza Zoldan, Janeta Sim, Woo Young Cho, Nahyun Jackson, Emily L. Mao, Shirley Schneider, Sabine Kim, Kwang-Soo Han, Min-Joon Lytton-Jean, Abigail K. R. Basto, Pamela Antonia Jhunjhunwala, Siddharth Heller, Daniel A. Kang, Jeon Woong Hartoularos, George C. Anderson, Daniel Griffith Langer, Robert Jensen, Klavs F. Adamo, Andrea, 1975- Lee, Jungmin, Ph. D. Massachusetts Institute of Technology |
| author_sort | Sharei, Armon Reza |
| collection | MIT |
| description | Intracellular delivery of macromolecules is a challenge in research and therapeutic applications. Existing vector-based and physical methods have limitations, including their reliance on exogenous materials or electrical fields, which can lead to toxicity or off-target effects. We describe a microfluidic approach to delivery in which cells are mechanically deformed as they pass through a constriction 30–80% smaller than the cell diameter. The resulting controlled application of compression and shear forces results in the formation of transient holes that enable the diffusion of material from the surrounding buffer into the cytosol. The method has demonstrated the ability to deliver a range of material, such as carbon nanotubes, proteins, and siRNA, to 11 cell types, including embryonic stem cells and immune cells. When used for the delivery of transcription factors, the microfluidic devices produced a 10-fold improvement in colony formation relative to electroporation and cell-penetrating peptides. Indeed, its ability to deliver structurally diverse materials and its applicability to difficult-to-transfect primary cells indicate that this method could potentially enable many research and clinical applications. |
| first_indexed | 2024-09-23T15:58:46Z |
| format | Article |
| id | mit-1721.1/80382 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T15:58:46Z |
| publishDate | 2013 |
| publisher | National Academy of Sciences (U.S.) |
| record_format | dspace |
| spelling | mit-1721.1/803822022-09-29T17:25:37Z A vector-free microfluidic platform for intracellular delivery Sharei, Armon Reza Zoldan, Janeta Sim, Woo Young Cho, Nahyun Jackson, Emily L. Mao, Shirley Schneider, Sabine Kim, Kwang-Soo Han, Min-Joon Lytton-Jean, Abigail K. R. Basto, Pamela Antonia Jhunjhunwala, Siddharth Heller, Daniel A. Kang, Jeon Woong Hartoularos, George C. Anderson, Daniel Griffith Langer, Robert Jensen, Klavs F. Adamo, Andrea, 1975- Lee, Jungmin, Ph. D. Massachusetts Institute of Technology Harvard University--MIT Division of Health Sciences and Technology Massachusetts Institute of Technology. Department of Biology Massachusetts Institute of Technology. Department of Chemical Engineering Massachusetts Institute of Technology. Department of Chemistry Massachusetts Institute of Technology. Department of Mechanical Engineering Massachusetts Institute of Technology. Laser Biomedical Research Center Massachusetts Institute of Technology. Spectroscopy Laboratory Koch Institute for Integrative Cancer Research at MIT Sharei, Armon Reza Zoldan, Janeta Adamo, Andrea Sim, Woo Young Cho, Nahyun Jackson, Emily L. Mao, Shirley Schneider, Sabine Lytton-Jean, Abigail K. R. Basto, Pamela Antonia Jhunjhunwala, Siddharth Lee, Jungmin Heller, Daniel A. Kang, Jeon Woong Hartoularos, George C. Anderson, Daniel Griffith Langer, Robert Jensen, Klavs F. Intracellular delivery of macromolecules is a challenge in research and therapeutic applications. Existing vector-based and physical methods have limitations, including their reliance on exogenous materials or electrical fields, which can lead to toxicity or off-target effects. We describe a microfluidic approach to delivery in which cells are mechanically deformed as they pass through a constriction 30–80% smaller than the cell diameter. The resulting controlled application of compression and shear forces results in the formation of transient holes that enable the diffusion of material from the surrounding buffer into the cytosol. The method has demonstrated the ability to deliver a range of material, such as carbon nanotubes, proteins, and siRNA, to 11 cell types, including embryonic stem cells and immune cells. When used for the delivery of transcription factors, the microfluidic devices produced a 10-fold improvement in colony formation relative to electroporation and cell-penetrating peptides. Indeed, its ability to deliver structurally diverse materials and its applicability to difficult-to-transfect primary cells indicate that this method could potentially enable many research and clinical applications. National Institutes of Health (U.S.) (Grant RC1 EB011187-02) National Institutes of Health (U.S.) (Grant DE01302) National Institutes of Health (U.S.) (Grant DE01651) National Institutes of Health (U.S.) (Grant EB00035) National Cancer Institute (U.S.) (Cancer Center Support Grant P30-CA14051) National Cancer Institute (U.S.) (Cancer Center Support Grant MPP-09Call-Langer-60) 2013-09-11T13:07:27Z 2013-09-11T13:07:27Z 2013-01 2012-10 Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 http://hdl.handle.net/1721.1/80382 Sharei, A., J. Zoldan, A. Adamo, W. Y. Sim, N. Cho, E. Jackson, S. Mao, et al. “A vector-free microfluidic platform for intracellular delivery.” Proceedings of the National Academy of Sciences 110, no. 6 (February 5, 2013): 2082-2087. https://orcid.org/0000-0001-5629-4798 https://orcid.org/0000-0001-7192-580X https://orcid.org/0000-0001-8046-2288 https://orcid.org/0000-0003-4255-0492 en_US http://dx.doi.org/10.1073/pnas.1218705110 Proceedings of the National Academy of Sciences Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf National Academy of Sciences (U.S.) PNAS |
| spellingShingle | Sharei, Armon Reza Zoldan, Janeta Sim, Woo Young Cho, Nahyun Jackson, Emily L. Mao, Shirley Schneider, Sabine Kim, Kwang-Soo Han, Min-Joon Lytton-Jean, Abigail K. R. Basto, Pamela Antonia Jhunjhunwala, Siddharth Heller, Daniel A. Kang, Jeon Woong Hartoularos, George C. Anderson, Daniel Griffith Langer, Robert Jensen, Klavs F. Adamo, Andrea, 1975- Lee, Jungmin, Ph. D. Massachusetts Institute of Technology A vector-free microfluidic platform for intracellular delivery |
| title | A vector-free microfluidic platform for intracellular delivery |
| title_full | A vector-free microfluidic platform for intracellular delivery |
| title_fullStr | A vector-free microfluidic platform for intracellular delivery |
| title_full_unstemmed | A vector-free microfluidic platform for intracellular delivery |
| title_short | A vector-free microfluidic platform for intracellular delivery |
| title_sort | vector free microfluidic platform for intracellular delivery |
| url | http://hdl.handle.net/1721.1/80382 https://orcid.org/0000-0001-5629-4798 https://orcid.org/0000-0001-7192-580X https://orcid.org/0000-0001-8046-2288 https://orcid.org/0000-0003-4255-0492 |
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