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 language | English (US) |
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Pages (from-to) | 5873-5881 |
Number of pages | 9 |
Journal | Small |
Volume | 12 |
Issue number | 42 |
DOIs | |
State | Published - Nov 9 2016 |
Externally published | Yes |
Keywords
- circulating tumor cells
- intracellular delivery
- microfluidics
- size-selective delivery
ASJC Scopus subject areas
- Engineering (miscellaneous)
- General Chemistry
- General Materials Science
- Biotechnology
- Biomaterials