Biophotonics and mechanobiology

Plasmonic biosensing, be it surface plasmon resonance (SPR) or localized surface plasmon resonance (LSPR), relies on the interaction of light photons with the electrons on the surface of nano-sized metals like Gold and Silver. Although the standard Au only layout has proven to be immensely beneficial in giving a real-time and label-free detection of analytes, with the evolving complexities of the biomolecules we need sophisticated arrangements. 

Thus, this project involves the usage of different 2D materials like Graphene and TMDCs and exploring their capabilities in enhancing the detection sensitivity and lowering the detection limit of the plasmonic sensors.

Cell growth and mass regulation are fundamental processes for all living organisms, yet they are poorly understood. To address this situation, we have invented a technology called Inertial Picobalance (or Cytomass Monitor), that allows measuring the mass of single or multiple cells in real time, enhancing our understanding of cell physiology. Considering that dysregulation of cell mass is a critical underlying force in the development of many diseases, understanding how cells regulate their mass has enormous potential to transform the way we diagnose, monitor and treat disease conditions such as cancer, diabetes, obesity, cardiovascular disease, ageing or infectious diseases.

Changes of intracellular water content and hence cell mass are linked with important cellular processes including gene expression, metabolism, cell proliferation, cell death and cell migration. Using a cutting-edge technology that we have developed, called Inertial Picobalance (or Cytomass Monitor), we are identifying the mass dynamics of single cells and cellular systems throughout key cellular processes. For example, we have discovered that mammalian cells fluctuate their mass quickly and that virus-infected cells show different cell mass dynamics. We aim to develop new screening assays and diagnostic methods based on cell mass sensing.

Cells respond and adapt to physical cues such as stiffness and rugosity of the environments they interact with. The biological function of biomolecules such as antibodies, and more complex structures such as viruses, is linked to their mechanical properties as well. We advance scanning probe microscopies and other nanotechnologies to accurately investigate such mechanobiological relationships. Our techniques allow the simultaneous acquisition of high-resolution images and flexibility maps directly in the liquid environment of biosamples.

High blood pressure (BP) is a major leading risk factor for disability, cardiovascular disease and kidney chronic disease - which is linked to 1 in 5 of all deaths. The lack of suitable technologies to reliably track and communicate BP to patients contributes to a large number of cases being undiagnosed. This prevents such patients from treatments and better lifestyle recommendations. For those who have been diagnosed, this results in limiting adherence to treatment or intervention. We aim to develop a method to accurately and non-invasively track the BP of patients in real-time from acoustic cardiac signals.

COVID-19 started as an initial localised spread and within months it became a global pandemic. With multiple mutants of the virus that is proving to be highly infectious, it is continuing to create havoc with many nations facing a deadly surge in the number of cases along with numerous lockdowns devastating the world economy.

We aim to model and design portable plasmonic biosensors that can detect the SARS-CoV-2 spike protein and thus fabricate fast and reliable plasmonic sensors that can be used for remote sensing.

Flow cytometry is an indispensable tool for the identification, classification, and enumeration of single cells/particles in biomedical applications like pathology, immunology, gene sequencing, chromosome sorting, biodefence, and disease diagnosis. However, the bulkiness and high cost limit their use in state-of-the-art research laboratories and high-end clinical settings.

We utilise hydrodynamic flow focusing to design inertial microfluidic devices that are able to achieve a stable single-position focusing for spherical particles/cells with diameters from 10 µm to 30 µm at fast flow rates (up to 700 µl/min). The miniature flow cytometer is integrated with tapered optical fibers for interrogating the focused cells/particles.

Conventional techniques used for drug delivery, disease progression, and prognosis rely on fluorescent beads, organic dyes, quantum dots (QDs), variable-sized-colored beads, etc. Apart from their photo-bleaching and toxicity limitations, these methods cannot be used as simultaneous carrier (biomolecules/drug/gene delivery) and signal providers (output/fluorescence signal).

We develop alternative non-toxic, stable, and biocompatible nanoassays that can be used as both biomolecule carriers and for signal analysis in gene therapy applications. We have shown the effectiveness of gold nanorods and biodegradable charged polyester-based vectors as gene delivery vehicles as well as signal providers in pancreatic cancer cells and chronic myeloid leukemia (CML) cells, respectively, in terms of gene transfection and gene knockdown efficiency.

Cancer cells have the ability to reprogram their energy metabolism in order to survive the often harsh conditions of the tumour microenvironment. This microenvironment of the tumour contributes greatly to the response of tumour cells.  Mechanics can affect intracellular signalling events, influencing carcinogenesis, cancer progression and the tumour response to therapy. Cancer cells have a highly stressful microenvironment, which is often mechanically stiff. The stiff tumour microenvironment can result in a variety of signalling events, which can affect critical cell survival pathways required for cancer progression and metastasis. Advance microscopy and nanomechanical tools will be used to determine the profiling of the matrix mechanics. Bioengineering platforms like hydrogels will be used as 3D models to examine the effects of mechanical stress on critical cell survival signalling pathways and their role in cancer progression and metastasis.

Functionalized nanomaterials are promising candidate for biomedical applications such as regenerative medicine, specifically for engineering of electroconductive tissues (e.g. cardiac, nerve or skeletal) that can be used for treatment of trauma, injuries or diseases. However, there are still knowledge gaps regarding the mechanistic understanding about the interactions between nanomaterials with electroactive tissues.  Understanding the mechanism of electrical conduction through cardiac tissue is essential for maintaining the function of the heart because conduction abnormalities are known to potentially lead to life-threatening arrhythmias. The materials will be characterised using the standard analytical techniques and will be tested for bioactivity using a range of in-vitro studies using cardiac cells (cardiomyocytes). The functionalised nanoparticles with electrical properties will hold enormous potential for developing medical devices for cardiovascular applications that can benefit and overcome socioeconomic and medical burden to a greater extent.

Peripheral nerve injuries can be devastating and can lead to long-term disability. It is a large scale problem and is estimated that on an average 560,000 procedures are performed for peripheral nerve injury per year in the U.S alone, causing a socioeconomic burden. Current treatments include direct nerve repair, autografts, allografts and nerve conduits. These are inadequate due to limited success rates, donor site morbidity, sacrifice of a functional nerve and difficult surgery. Functional regeneration of peripheral nerve is hindered by factors such as inadequate extracellular matrix formation and insufficient/reduced neurotrophic factors.

In this project, we will utilise engineered biomaterials and nanomaterials to mimic the 3D microenvironment and explore the underlying mechanisms responsible for modulating the process of nerve repair/regeneration.

One of the challenges in biomedical engineering is to understand how cells interact with the surrounding environment and the effects of that environment on the molecular mechanisms of the cells. Understanding their mechanisms is vital to design innovative instructive materials that are capable of directing cells down a pathway of tissue organisation and formation. Confocal microscopy with high content analysis (HCA) is a new technology that is being adopted in the field of bioengineering, health technologies and cell biology research. The combination of confocal microscopy and high content analysis can enable quantitative measurement of cellular activity to a greater extent. Simultaneous quantification of these changes along with high-resolution image acquisition can decipher some of the innate cellular responses with greater precision and throughput than traditional confocal microscopy.

The project involves fully integrated confocal imaging, acquisition and the simultaneous high throughput quantitative analysis of various cell functions.

Cardiovascular disease (CVD) refers to all diseases involving the heart and circulation, including coronary artery disease, stroke, atrial fibrillation and most importantly atherosclerosis. It is the leading cause of cardiovascular deaths, accounting for around 30% of all deaths in Australia.

Atherosclerosis is the main underlying factor behind CVD and it involves the gradual build-up of plaque within the artery wall. Plaques are made up of lipoproteins, smooth muscle cells, macrophages and other substances that interact with each other and begin to coalesce. This project is focused on unravelling novel signalling molecules that are linked to atherosclerosis and bone loss and understand the role of key factors behind these diseases thus providing more fundamental information that can lead to the development of therapeutic solutions.

Most of the existing fluorescent probes used for imaging and sensing in cancer theranostics comprise of Cadmium-based quantum dots or QDs, which are known to degrade in the biological environment and cause serious toxicity issues.

We synthesise uniform-sized and aqueous dispersible nitrogen and sulfur co-doped carbon dots which exhibit excitation-dependent and pH-dependent photoluminescence properties in the visible range. With a high photoluminescence quantum yield and strong photostability in a high ionic strength environment, we demonstrate the versatility of the carbon dots by employing them as low-toxicity fluorescent labels and for semi-quantitative and selective sensing of Fe3+ in cancer cells.

Cigarette smoke is a dominant risk factor for chronic obstructive pulmonary disease (COPD) and lung cancer. However, the underlying molecular mechanisms of cigarette smoke-induced malignant transformation of bronchial epithelial cells remain unclear. Microfluidic 3D culture system is a practical tool for in vitro modelling of complex human physiology mimicking the carcinogenesis of epithelial tissue in a structurally appropriate context.

Our studies aim to establish lung-on-a-chip system as a model of a breathing lung containing vascular endothelium and bronchial epithelium, to explore the possible mechanistic link between cigarette smoke and COPD, and the subsequent malignant transformation of bronchial epithelium.

Reconstruction of full-thickness human skin equivalents with physiologically-relevant cellular and matrix architecture is gaining importance as an in-vitro tool for basic research in pharmaceutical, toxicological, and cosmetic industries.

Traditional static culture substrates used for the reconstruction of human skin equivalents do not sufficiently satisfy the requirements of mechanical forces and a dynamic flow system to provide necessary mechanistic signals and continuous supply and/or drainage of nutrients and metabolites.

We utilise fibrin-based dermal matrix in a well-controlled microfluidic environment with dynamic perfusions to develop human skin equivalents. We are particularly interested to study improved epidermal differentiation and enhanced barrier function in this dynamic system.

Technological advances in stem cell therapy are being increasingly exploited as a promising tool for the renewal of cardiac cells and the treatment of heart diseases. In-vitro cardiovascular models based on monolayer cultures under static conditions cannot fully mimic natural cardiac physiology due to random orientation of cells, manual media exchanges and subsequently, lack of lineage commitment. 

We aim to engineer 3D cardiac organoids that would enable the growth of cardiac cells in conditions similar to in vivo conditions. Perfusion microsystems would enable controlled supply of nutrients and metabolites and provide a better understanding of heart diseases.

Assessing biomarkers in skin interstitial fluid (ISF) is an emerging technique for disease diagnosis and prognosis. A micro-needle patch is an ideal platform to extract ISF from the skin due to its pain-free and easy-to-administer features. However, the relatively slow ISF extraction rate by the micro-needle patch impedes timely metabolic analysis and limits its usage in biomedical applications

We fabricate a novel micro-needle patch that can rapidly extract ISF and subsequently develop a wearable biosensor device integrated with the micro-needle patch for detecting physiological signals of the user in real-time in a continuous and pain-free manner.

Triboelectric nanogenerator (TENG) is regarded as a promising mechanical energy-harvesting device, which can generate electricity from low frequency motions, such as human activities. Recent studies have demonstrated various applications of TENG as power sources in wearable bioelectronics and bio-devices including e-skin, smartwatch/wristband, and micro drug delivery devices.

Interestingly, TENG generates a high voltage (from tens to thousands of volts) and low current (from nano to microamperes) output, which is harmless to humans. These unique characteristics comply with the needs of certain biomedical applications, such as electroporation. We develop TENG-powered biomedical systems for transdermal drug delivery and electricity-triggered controlled drug release.