Among the many methods of intracellular delivery, cell size-selective delivery is particularly applicable to cancer research and therapeutics where tumor cells tend to be larger than blood cells and selective manipulation of a single cell-type while minimally affecting the other cells in a heterogeneous mixture is important. In this study, cell size-selective delivery is achieved using a novel microfluidic device with 75 parallel channels through which cells are pushed under nitrogen pressure. The cells undergo deformation as they transit through the channels, which results in temporary disruption of the cell membrane to facilitate delivery of material into the cytoplasm. For each cell size, there is a specific channel width for which optimal cell viability and fluorophore delivery is achieved, with smaller cells requiring narrower channels. When two cells of different sizes are mixed in solution, the channel width for optimal cell viability and fluorophore delivery for each cell type remains the same, and larger cells can achieve fluorophore delivery at a significantly higher percentage than smaller cells at the former's optimal channel width. One possible application for this technology is tagging circulating tumor cells, and we have been able to selectively deliver fluorophores into tumor cells when spiked into whole human blood with 91% specificity. We were also able to isolate pancreatic tumors cells from a patient's blood sample that matched the genotype of the patient's primary pancreatic tumor. Intracellular delivery of materials has become increasingly important as we delve deeper into understanding cellular processes and developing targeted therapies, and with this device, selective delivery can be achieved in a vector-free environment and without dependence on cell-surface receptors.

Citation Format: May Tun Saung, Armon Sharei, Viktor Adalsteinsson, Andrew Liss, Nahyun Cho, Tushar Kamath, Camilo Ruiz, Jesse Kirkpatrick, Robert Langer, Christopher Love, Klavs Jensen. Cell size-specific intracellular delivery. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5538A. doi:10.1158/1538-7445.AM2015-5538A