In recent nanobiotechnology developments, a wide variety of functional nanomaterials and engineered biomolecules have been created, and these have numerous applications in cell biology. For these nanomaterials to fulfill their promises completely, they must be able to reach their biological targets at the subcellular level and with a high level of specificity. Traditionally, either nanocarrier- or membrane disruption-based method has been used to deliver nanomaterials inside cells; however, these methods are suboptimal due to their toxicity, inconsistent delivery, and low throughput, and they are also labor intensive and time-consuming, highlighting the need for development of a next-generation, intracellular delivery system. This study reports on the development of an intracellular nanomaterial delivery platform, based on unexpected cell-deformation phenomena via spiral vortex and vortex breakdown exerted in the cross- and T-junctions at moderate Reynolds numbers. These vortex-induced cell deformation and sequential restoration processes open cell membranes transiently, allowing effective and robust intracellular delivery of nanomaterials in a single step without the aid of carriers or external apparatus. By using the platform described here (termed spiral hydroporator), we demonstrate the delivery of different nanomaterials, including gold nanoparticles (200 nm diameter), functional mesoporous silica nanoparticles (150 nm diameter), dextran (hydrodynamic diameters between 2-55 nm), and mRNA, into different cell types. We demonstrate here that the system is highly efficient (up to 96.5%) with high throughput (up to 1 × 106 cells/min) and rapid delivery (∼1 min) while maintaining high levels of cell viability (up to 94%).
Bibliographical noteFunding Information:
A.C. acknowledges the Samsung Research Funding and Incubation Center for Future Technology (grant no. SRFC-IT1802-03) to conduct all experimental studies. S.H. and A.S. gratefully acknowledge the Okinawa Institute of Science and Technology Graduate University, and financial support from the Cabinet Office, Government of Japan, and funding from the Japan Society for the Promotion of Science (grant nos. 17K06173, 18K03958, and 18H01135) with computational resources provided by the Scientific Computing section of Research Support Division at OIST for numerical studies. The authors would like to thank Prof. Ssang-Goo Cho at Konkuk University, Prof. Jae-Yong Park and Yeonju Bae at Korea University, Hyun Ji An at the University of Seoul, and all members of the Biomicrofluidics Laboratory at Korea University for their technical support and useful discussions. Provisional patents have been filed by the authors’ institutions.
© 2020 American Chemical Society.
- cell transfection
- inertial microfluidics
- intracellular delivery
- macromolecule delivery
- nanoparticle delivery
ASJC Scopus subject areas
- General Materials Science
- General Engineering
- General Physics and Astronomy