Developing high-speed surface-enhanced Raman bioimaging platforms
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Citation
Abstract
Surface-enhanced Raman scattering (SERS) is an emerging technique with great sensitivities gained from plasmonic enhancement and many advantages inherited from Raman spectroscopy, including direct detection of the intrinsic molecular fingerprint spectroscopic information from diverse molecules, superior multiplexing capabilities due to narrow Raman bandwidths, high photostability of SERS signals, and low background from biological tissues and water. Therefore, SERS imaging has been extensively utilized as a powerful bioimaging platform to visualize biocomponents spanning from biomolecules to entire organisms, enabling broad biomedical applications such as observing subcellular or cellular structures, mapping intercellular connections, probing tissue complexities, and in vivo imaging of organs or detection of tumors, etc. Even though SERS has successfully demonstrated its capabilities as a versatile bioimaging platform through many exciting biomedical applications, SERS imaging suffers from a main drawback by presenting a relatively slow imaging speed of typically 1 to 10 seconds per spectrum, which largely limits its applications such as probing fast cellular dynamics or large-area mapping of biological tissues.
To address the above challenges, we devoted our efforts in developing high-speed surface-enhanced Raman-based bioimaging platforms. Firstly, we developed gap-enhanced gold nanodumbbells that presented excellent SERS performances as ultrabright SERS nanoprobes to benefit high-speed SERS imaging. We successfully achieved single-particle detection of individual gold nanodumbbells with an imaging speed as fast as 0.1 seconds per spectrum. Secondly, by carefully evaluating the optical mechanism of SERS, which is a surface-enhanced spontaneous Raman process, we were inspired to develop surface-enhanced coherent anti-Stokes Raman scattering (SE-CARS) spectroscopy. The introduction of the coherent Raman process increased the imaging speed by at least 2 orders, enabling us to achieve single-particle SE-CARS detection within 1 millisecond per spectrum. Lastly, we developed the wide-filed surface-enhanced coherent anti-Stokes Raman scattering (WISE-CARS) microscopy that enabled parallel collection of over 1 million spectra within 1 second for cellular bioimaging and biomolecule detection.
Through strategically improving Raman imaging speed step by step by a combination of sophisticated Raman nanotag design, the introduction of coherent Raman spectroscopy, and advanced instrumentation development, we successfully demonstrated that an overall imaging speed increase by nearly a million times over SERS could be achieved. The development of high-speed surface-enhanced Raman bioimaging platforms would open opportunities for more fascinating biomedical applications where rapid imaging speed is strongly required.
Description
2024
License
Attribution 4.0 International