Alex K. Shalek
a, Jacob T. Robinson
a, Ethan S. Karp
a, Jin Seok Lee
a,2, Dae-Ro Ahn
b, Myung-Han Yoon
a, Amy Sutton
a, Marsela Jorgolli
c, Rona S. Gertner
a, Taranjit S. Gujral
a, Gavin MacBeath
a, Eun Gyeong Yang
a,b,1 and Hongkun Park
a,c,1
aDepartment of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138,
bLife Sciences Research Division, Korea Institute of Science and Technology, 39-1 Hawolgok-Dong, Seongbuk-Gu, Seoul, Korea 136-791, and
cDepartment of Physics, Harvard University, 12 Oxford Street, Cambridge, MA 02138
2Present address: Department of Chemistry, Sookmyung Women’s University, Seoul, Korea
Edited by Peidong Yang, UC Berkeley, and accepted by the Editorial Board December 3, 2009 (received for review August 17, 2009)
Abstract
A generalized platform for introducing a diverse range of biomolecules into living cells in high-throughput could transform how complex cellular processes are probed and analyzed. Here, we demonstrate spatially localized, efficient, and universal delivery of biomolecules into immortalized and primary mammalian cells using surface-modified vertical silicon nanowires. The method relies on the ability of the silicon nanowires to penetrate a cell’s membrane and subsequently release surface-bound molecules directly into the cell’s cytosol, thus allowing highly efficient delivery of biomolecules without chemical modification or viral packaging. This modality enables one to assess the phenotypic consequences of introducing a broad range of biological effectors (DNAs, RNAs, peptides, proteins, and small molecules) into almost any cell type. We show that this platform can be used to guide neuronal progenitor growth with small molecules, knock down transcript levels by delivering siRNAs, inhibit apoptosis using peptides, and introduce targeted proteins to specific organelles. We further demonstrate codelivery of siRNAs and proteins on a single substrate in a microarray format, highlighting this technology’s potential as a robust, monolithic platform for high-throughput, miniaturized bioassays.
intracellular delivery, microarray, high-throughput bioassay, nanobiotechnology
Footnotes
1To whom correspondence should be addressed
Author contributions: A.K.S., J.T.R., G.M., E.G.Y., and H.P. designed research; A.K.S., J.T.R., E.S.K., J.S.L., D.-R.A., M.-H.Y., A.S., M.J., R.S.G., T.S.G., and E.G.Y. performed research; A.K.S., J.T.R., M.-H.Y., and E.G.Y. analyzed data; A.K.S., J.T.R., E.S.K., G.M., E.G.Y., and H.P. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission. P.Y. is a guest editor invited by the Editorial Board.
This article contains supporting information online at
www.pnas.org/cgi/content/full/0909350107/DCSupplemental.