A Size‐Selective Intracellular Delivery Platform. Issue 42 (4th September 2016)

• Record Type: Journal Article
• Authors: Saung, May Tun; Sharei, Armon; Adalsteinsson, Viktor A.; Cho, Nahyun; Kamath, Tushar; Ruiz, Camilo; Kirkpatrick, Jesse; Patel, Nehal; Mino‐Kenudson, Mari; Thayer, Sarah P.; Langer, Robert; Jensen, Klavs F.; Liss, Andrew S.; Love, J. Christopher
• Is Part Of: Small. Volume 12:Issue 42(2016)
• Page Start: 5873
• Page End: 5881
• Publication Date: 2016-09-04
• Subjects: circulating tumor cells -- intracellular delivery -- microfluidics -- size‐selective delivery; Nanotechnology -- Periodicals; Nanoparticles -- Periodicals; Microtechnology -- Periodicals; 620.5
• DOI: 10.1002/smll.201601155
• Languages: English
• ISSNs: 1613-6810

Abstract

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. Abstract : Mechanical force in a microfluidic device induces transient plasma membrane disruption to deliver payload to the cytoplasm of cells. This platform allows for the use of cell size to facilitate subset selection in a heterogeneous population of cells. The applicability of this method is demonstrated with the identification and analysis of circulating tumor cells of a patient with pancreatic cancer.