A Size-Selective Intracellular Delivery Platform

May Tun Saung, Armon Sharei, Viktor A. Adalsteinsson, Nahyun Cho, Tushar Kamath, Camilo Ruiz, Jesse Kirkpatrick, Nehal Patel, Mari Mino-Kenudson, Sarah P. Thayer, Robert Langer, Klavs F. Jensen, Andrew S. Liss, J. Christopher Love

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)5873-5881
Number of pages9
JournalSmall
Volume12
Issue number42
DOIs
StatePublished - Nov 9 2016

Keywords

  • circulating tumor cells
  • intracellular delivery
  • microfluidics
  • size-selective delivery

ASJC Scopus subject areas

  • Biotechnology
  • Biomaterials
  • Chemistry(all)
  • Materials Science(all)

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  • Cite this

    Saung, M. T., Sharei, A., Adalsteinsson, V. A., Cho, N., Kamath, T., Ruiz, C., Kirkpatrick, J., Patel, N., Mino-Kenudson, M., Thayer, S. P., Langer, R., Jensen, K. F., Liss, A. S., & Love, J. C. (2016). A Size-Selective Intracellular Delivery Platform. Small, 12(42), 5873-5881. https://doi.org/10.1002/smll.201601155