Research

Digital assays - Sensitive Biosensors for the Digital Age

In collaboration with Professor Richard Tilley

The detection of disease biomarkers (such as proteins, DNA fragments and RNAs) in biological fluid is essential for the early detection of diseases. One of the primary challenges is the low concentration (typically in the femtomolar range) of the biomarkers. We are looking into new approaches to construct digital biosensors based on plasmonic nanoparticles. With the help of a dark-field optical microscope, we can look at the scattering arising from individual nanoparticles. The wide field nature of this measurement allows for the simultaneous characterization of thousand nanoparticles. When a biochemical sensing reaction is performed, the optical signature of the nanoparticle is altered thereby leading to change in the colour of the nanoparticle. By setting a threshold, we digitalize the data to 0 (unreacted) and 1 (reacted) nanoparticles. Our aim is to push this approach for the detection of individual biomarkers on individual nanoparticles.

Detection of Single Biomolecules using Magnetic Nanoparticles and Nanopore Sensors

A typical biosensor detects many molecules to give the concentration of species. Nanopores, which are commonly proposed for DNA sequencing, can detect single molecules and give concentration of species by counting many single molecules. This avoids the need for calibration however, detection limits are not as low as one expects because of the time taken for the molecules to find the nanopores. We have solved this problem by developing a new type of nanopore, referred to as a nanopore blockade sensor. In this system, antibody magnetic nanoparticles capture the analyte of interest and bring it to the nanopore. The nanomodified nanopores article then blocks the nanopore to give a single molecule measurement. An additional benefit is the nanopore blockade sensors can operate in complex biological fluids. This project will involve developing the next generation of this exciting single molecule sensor.

3D printing of cells for improved tumour models and drug assays

In collaboration with Australian Centre for NanoMedicine

Our current understanding of cancerous tumours is heavily based on in vivo experiments in animals or in vitro experiments on tissue culture plates. To date, few techniques exist that can satisfactorily recreate the tumour environment in vitro in 3-Dimensions. Such models would allow biologists to better understand the effect of spatial organisation of biomolecules on cell behaviour. Of particular interest are molecules that trigger cancer cell metastasis, or invasion, to other parts of the body.  In our lab we are developing materials that can recreate the 3D tumour environment, made from polymers that provide a matrix for cells to attach to (see figure). In the proposed project, the polymers will be modified to include a peptide (protein-based) crosslink that stabilises the structure. Such protein-based regions are susceptible to degradation by specific types of enzymes (proteases) released by cancer cells when they invade surrounding tissue. The new materials developed in this project will be used as an extracellular matrix for the 3D printing of cells in collaboration with a 3D printing start-up company.

The synthesis of electrocatalysts for fuels cells that mimic enzyme structure

In collaboration with Professor Richard Tilley

Electrocatalysts are important is applications as broad as fuels cells to sensors to production of fine chemicals. There are however a clear differences between a man made metallic electrocatalyst and a biological catalyst (an enzyme). In man made catalyst the catalytic sites are on the surface of the particle and the entire particle is conducting. However recent work in Science suggests catalytic sites in depressions may in fact be more active.  In depressions or clefts are where most catalytic sites are located in enzymes. In this way the catalytic site is separated from the reactant solution which allows the chemical environment to be different from the bulk solution and the site to be protected from other species in solution. In this project we will synthesize catalytic nanoparticles for the oxygen reduction reaction that mimic enzyme structure by having the catalytic sites buried inside the particle but accessible via a small channel. Hence this work will focus on making core-shell nanoparticles, electron microscopy characterisation and performing electrocatalytic experiments with them.