Surface plasmon enhanced fluorescence for biological imaging : from visible to short-wave infrared

Abstract

Fluorescence imaging offers high spatio-temporal resolution, low radiation dosage exposure, and low cost among all the available imaging modalities, for example, magnetic resonance imaging, computerized tomography and positron emission tomography. Imaging probes of high emissivity and photostability are the key to achieving fluorescence imaging with high signal-to-background ratio (SBR). One promising approach to developing highly bright and stable imaging probes is through surface plasmon enhanced fluorescence. In the first part of the thesis, we develop a fluorescent probe with high site-specificity and emission efficiency by exploiting the targeting-specificity of M13 virus and co-assembling plasmonic nanoparticles and visible dye molecules on the viral capsid. Practical factors controlling fluorescence enhancement, such as nanoparticle size and dye-to-nanoparticle distance, are studied in this project. Lastly, the highly fluorescent probe is applied for in vitro staining of E.

coli. The methodology in this work is amendable to developing a wide range of affinity-targeted fluorescent probes using biotemplates. Compared to visible and near infrared spectrum, short-wave infrared (SWIR, 900-1700 nm) spectrum promises high spatial resolution and deep tissue penetration for fluorescence imaging of biological system, owning to low tissue autofluorescence and suppressed tissue scattering at progressively longer wavelengths. In the second part of the thesis, a bright SWIR imaging probe consisting of small SWIR dyes and gold nanorods is developed for in vivo imaging. Fluorescence enhancement is optimized by tuning the dye density on the gold nanorod surface. The SWIR imaging probes are applied for in vivo imaging of ovarian cancer. The effect of targeting modality on intratumor distribution of the imaging probes is studied in two different orthotopic ovarian cancer models.

Lastly, we demonstrate that the plasmon enhanced SWIR imaging probe has great potential for fluorescence imaging-guided surgery by showing its capability to detect submillimeter-sized tumors. Apart from enhancing the SWIR down-conversion emission above, surface plasmon enhanced SWIR up-conversion emission is another promising approach to achieving "autofluorescence-free" imaging with minimal tissue scattering. In the third part of the thesis, we use gold nanorods to enhance the up-conversion emission of small SWIR dyes. The mechanism of surface plasmon enhanced up-conversion emission is studied. The up-conversion fluorescence shows much higher SBR than down-conversion fluorescence in non-scatting biological solution and scatting medium. Lastly, we demonstrate in vivo imaging for the first-time using SWIR up-conversion fluorescence with exceptional image contrast.