Current clinical diagnosis of most epithelial cancer typically involves invasive biopsies on suspicious lesions which may present health risks and psychological trauma to patients. Novel optical imaging such as optical coherence tomography (OCT) and reflectance confocal endomicroscopy (RCM) have the potential of performing noninvasive optical biopsies.

Although OCT and RCM are able to provide cellular resolution to image the structural integrity of tissues in vivo, their optical contrast between normal, early dysplastic and neoplastic tissues is often too low to be of any significant clinical value. Furthermore, these imaging techniques are unable to image the biomolecular changes associated with carcinogenesis which can provide earlier diagnosis compared to structural abnormalities.

The main objective of this research is to develop and investigate the use of gold nanoshells as cancer-specific probes to address the limitations of these imaging techniques for early epithelial carcinoma. The use of gold nanoshells could increase the optical contrast between normal and early suspicious lesions and also simultaneously provide useful molecular specific information for the diagnosis of these lesions in vivo when used with novel reflectance confocal and OCT imaging.

Phase contrast imaging has been an established technique in microscopy and a popular assisting tool in biological and biomedical research. However it has limited capability in producing quantitative data, thus images can only be used for qualitative assessment so far.

The project of quantitative phase imaging focuses on improving and innovating modalities such as Differential Interference Microscopy (DIC) and Digital Holographic Microscopy (DHM). The aim is to capture minute structures of unstained biological samples in three-dimensional space using intrinsic contrast generated from variations of the object’s refractive index. With a potential axial sensitivity down to nanometers and no exogenous reagents used, the 3D quantitative phase data will be significant in interpreting many of the biophysical properties of living cells and organisms.

Techniques in diffractive solid immersion lens (DSIL) and refractive solid immersion lens (RSIL) for resolution enhancement in optical imaging are currently being developed. The field of application is in optical failure analysis techniques of semiconductor devices, for example, laser induced techniques (TIVA).

Current project uses diffraction theory for high aperture focusing in modeling refractive solid immersion lens.

Surface plasmon resonance (SPR) are due to coherent oscillations of free electrons in a metal, which result in localized areas of intense elecric fields. This effect may be applied to imaging, e.g. using the surface plasmon-coupled emission effect to achieve better background suppression and higher signal-to-noise ratio, or using gold nanoparticles as contrast agents for deep tissue imaging.

Gold is normally used to obtain SPR as it is not toxic to cells. Furthermore, gold nanoparticles do not suffer from photobleaching, unlike fluorophores. This project focuses on the application of surface plasmon resonance to microscopy as well as in investigating the use of gold nanoparticles to obtain information about the microenvironments of tissues.

Spatiotemporal measurements from microscopy can lead to precise and quantitative measurements of biological processes. Using special techniques such as polarization microscopy, Differential Interference Contrast (DIC), and Differential Phase Contrast (DPC) in combination with fluorescence methods, tracking of proteins and their interactions in live cells is possible. The current project aims to develop quantitative phase imaging methods, such as Asymmetric Illumination based Differential Phase Contrast (AIDPC), suitable for measurement of spatial and temporal changes in cellular morphology during fast biological events such as mitosis.

This approach allows accurate measurement of mitotic timing without label. Complementary fluorescence imaging approaches can be used to visualize components of mitotic machinery. This is a collaborative project with Prof. Caroline Lee from the National Cancer Centre.