A vector-free microfluidic platform for intracellular delivery

• Main Authors: Sharei, Armon Reza (Contributor), Zoldan, Janeta (Contributor), Sim, Woo Young (Contributor), Cho, Nahyun (Contributor), Jackson, Emily L. (Contributor), Mao, Shirley (Contributor), Schneider, Sabine (Contributor), Kim, Kwang-Soo (Author), Han, Min-Joon (Author), Lytton-Jean, Abigail K. R. (Contributor), Basto, Pamela Antonia (Contributor), Jhunjhunwala, Siddharth (Contributor), Heller, Daniel A. (Contributor), Kang, Jeon Woong (Contributor), Hartoularos, George C. (Contributor), Anderson, Daniel Griffith (Contributor), Langer, Robert (Contributor), Jensen, Klavs F. (Contributor), Adamo, Andrea 1975- (Author), Lee, Jungmin, Ph. D. Massachusetts Institute of Technology (Author)
• Other Authors: Harvard University- (Contributor), Massachusetts Institute of Technology. Department of Biology (Contributor), Massachusetts Institute of Technology. Department of Chemical Engineering (Contributor), Massachusetts Institute of Technology. Department of Chemistry (Contributor), Massachusetts Institute of Technology. Department of Mechanical Engineering (Contributor), Massachusetts Institute of Technology. Laser Biomedical Research Center (Contributor), Massachusetts Institute of Technology. Spectroscopy Laboratory (Contributor), Koch Institute for Integrative Cancer Research at MIT (Contributor), Adamo, Andrea (Contributor), Lee, Jungmin (Contributor)
• Format: Article
• Language: English
• Published: National Academy of Sciences (U.S.), 2013-09-11T13:07:27Z.
• Subjects: Article
• Online Access: Get fulltext

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)