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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Bibliographic Details
Main Authors: 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
Other Authors: Harvard University--MIT Division of Health Sciences and Technology
Format: Article
Language:en_US
Published: National Academy of Sciences (U.S.) 2013
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
Description
Summary: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.