Application of photonic nanomaterials for diagnostics

Nanotechnology has quickly gained recognition in biomedical imaging and diagnostics by harnessing unique properties of nanomaterials, including programmability of their physical and chemical characteristics, such as size, shape, surface-to-volume ratio, and surface chemistry, allowing programmed delivery of therapeutics and diagnostics (theranostics) cargo. Photoluminescent nanoparticles are a mainstay of theranostics owing to multimodalities and the potential to engineer their optical properties, including brightness, emission lifetime, and photostability. The deployment of photoluminescent nanoparticles in optical imaging provides informative, non-destructive, and affordable means to assess the physiological condition and functionality of biological systems with unprecedented spatial and temporal resolution. However, the observation, analysis, and quantification of the photoluminescent signatures of biomolecular markers may be hindered by unwanted background due to scattered excitation light and autofluorescence from biological cells and tissues.

The development of the next-generation photoluminescent nanoparticles to enable high-contrast imaging on the background of turbid, chromogenic biological tissues represents the key aim of my PhD project. My thesis reports developed lanthanide-doped nanoparticles which have excitation and emission bands within the second tissue optical transparency window. The particles have long emission lifetimes, which enables suppression of the optical background by implementing a time-gating detection scheme. This scheme, realised by means of an optoelectronic device, is proprietary (patent pending), featuring operation in the Megahertz range, and represents a breakthrough in the field.

To address the problem of simultaneous imaging of multiple biomarkers in highly scattering biological media, I contributed to the characterization of ruby nanocrystals with tunable emission lifetime (tau-rubies). Their multiplexing and demultiplexing capabilities were demonstrated in a biological system, when several biomarkers were labelled with different tau-ruby markers.

The toxicological impact of photoluminescent nanoparticles on biological systems raises concerns, especially if they degrade slowly (reportedly, up to a year of residence in the organism), and even stop degrading in biological fluids, as I found by directly observing silicon nanoparticles by using a custom-built photoacoustic measurement system. To restore the biodegradation, my colleagues and I developed a specific polymer coating, which was deployed to demonstrate 10-fold improved nanomedicine accumulation in the xenograft tumour by blocking the mononuclear phagocyte system.

I believe that the work reported in this PhD thesis will support the use of photoluminescent nanomaterials for biomedical applications.