Advanced plasmonic technologies for multi-scale biomedical imaging.

The use of imaging technologies has been critical in deciphering biological phenomena, structures, and mechanisms across a wide range of spatial scales. The spatial resolution of traditional imaging modalities cannot meet the needs of high-precision research and diagnosis in biomedical fields. Plasmon resonance is the light-matter interaction that allows localizing far-field radiation in the near field with an intense electromagnetic field, enhancing the nanometric ablation, elastic/inelastic scattering of the adsorbate, and photoluminescence of the fluorophore nearby. Further, plasmon resonance scattering of nanoparticles can sensitively indicate the local environmental changes. This is accomplished by combining the spatially resolved capability with molecular spectrometry techniques such as Raman, infrared, fluorescence, etc., leading to a series of excellent imaging techniques to interrogate diverse biological processes from the tissue to subcellular level. In this tutorial review, we first provide the fundamental aspects of plasmonics. Then we give a systematic discussion of the working principle of these plasmon-based imaging techniques with an emphasis on the achievable spatial resolutions: surface-enhanced Raman spectroscopy (micrometre to nanometre), tip-enhanced ablation and ionization mass spectrometry (submicrometre), scattering-type scanning near-field optical microscopy (nanometre), tip-enhanced Raman spectroscopy (nanometre), tip-enhanced fluorescence spectroscopy (nanometre), and plasmon/molecular ruler microscopy (nanometre to angstrom). We also review the recent developments of the bioimaging applications of these techniques and expect that the plasmon-based techniques will not only pave a new way to decipher mysteries in life sciences but also hold great potential to be extended from fundamental research studies to real-life biomedical applications.