High Resolution Live Cell Raman Imaging Using Subcellular
Organelle-Targeting SERS-Sensitive Gold Nanoparticles with Highly
Narrow Intra-Nanogap
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Abstract
We
report a method to achieve high speed and high resolution live cell
Raman images using small spherical gold nanoparticles with highly
narrow intra-nanogap structures responding to NIR excitation (785
nm) and high-speed confocal Raman microscopy. The three different
Raman-active molecules placed in the narrow intra-nanogap showed a
strong and uniform Raman intensity in solution even under transient
exposure time (10 ms) and low input power of incident laser (200 μW),
which lead to obtain high-resolution single cell image within 30 s
without inducing significant cell damage. The high resolution Raman
image showed the distributions of gold nanoparticles for their targeted
sites such as cytoplasm, mitochondria, or nucleus. The high speed
Raman-based live cell imaging allowed us to monitor rapidly changing
cell morphologies during cell death induced by the addition of highly
toxic KCN solution to cells. These results strongly suggest that the
use of SERS-active nanoparticle can greatly improve the current temporal
resolution and image quality of Raman-based cell images enough to
obtain the detailed cell dynamics and/or the responses of cells to
potential drug molecules