We demonstrate high contrast optical-resolution photoacoustic
microscopy
(OR-PAM) imaging by using biocompatible, indirect band gap silicon
nanoparticles (SiNPs) as contrast agents. The SiNPs were synthesized
by high-energy ball milling of crystalline silicon wafers, followed
by hydrosilylation with bifunctional olefinic ligands to enable water
solubility and bioconjugation. When uniformly dispersed in water,
the SiNPs with an average particle size of about 114 nm showed remarkably
high extinction coefficients, more than 2 × 1010 M–1 cm–1, from the visible to near-infrared
spectral range. For the first OR-PAM imaging demonstration, the SiNPs
were microinjected to live zebrafish embryonic cells. As the embryo
developed, the distribution of the cells carrying the SiNPs can be
clearly traced by the spread of the photoacoustic signals. Second,
photoacoustic-fluorescence dual-modality imaging was demonstrated
on live zebrafish larvae which were microinjected with a mixture of
the SiNPs and dextran-rhodamine dyes. Due to the large difference
in size, the two agents exhibited very different biodistributions
after being injected at the same instant. Third, immuno-photoacoustic
imaging, as an autofluorescence-free alternative to the conventional
immunofluorescence imaging, was demonstrated on SKOV-3 cancer cells
immunostained with the anti-HER2-conjugated SiNPs. Lastly, advantages
of the SiNPs compared to other photoacoustic contrast agents were
characterized and discussed.
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