Efficient drug and biomolecular delivery into cells is an important area of biomedical research. Intracellular delivery relies on porating cell membranes to allow exterior molecules to enter the cell efficiently and viably. Various methods, including optoporation, electroporation, and viral techniques, can deliver molecules to cells, but come with significant drawbacks such as low efficiency, low throughput, and low viability. We present a new laser-based delivery method that uses laser pulses to excite plasmonic, Titanium Nitride (TiN) microstructures for cell poration and offers high efficiency, throughput, and viability. TiN is a promising plasmonic material for laser-based delivery methods due to its high levels of hardness and thermal stability. We fabricate these microstructures by sputtering thin films of TiN on patterned sapphire substrates. We then optimize plasmonic enhancement and stability by investigating different fabrication conditions. We deliver dye molecules, siRNA, and microspheres to cells to quantify poration efficiency and viability by using flow cytometry and by imaging the target cells at defined time intervals post laser irradiation. Additionally, we study temperature effects via simulations and experiments, as well as oxidation of the TiN films over time. We also use scanning electron microscopy (SEM) techniques to study microstructure damage and cell adhesion. Overall, TiN presents a promising opportunity for use as a reusable material in future biomedical devices for intracellular biomolecular delivery and regenerative medicine.
Alexander J. Raun, Nabiha Saklayen, Christine M. Zgrabik, Daryl I. Vulis, Marinna Madrid, Weilu Shen, Evelyn L. Hu, and Eric Mazur, "Reusable titanium nitride plasmonic microstructures for intracellular delivery (Conference Presentation)," Proc. SPIE 10094, Frontiers in Ultrafast Optics: Biomedical, Scientific, and Industrial Applications XVII, 100940C (Presented at SPIE LASE: January 29, 2017; Published: 21 April 2017); https://doi.org/10.1117/12.2253118.5389862312001.
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