Diagnostics & Imaging
Current ACN projects focussed on Diagnostics & Imaging
3D printing of cell cultures
In collaboration with Inventia Life Science
3D printed spheroid.
Cell culture has for many years been performed in 2 dimensions on cell culture dishes but in recent years it has become more accepted that cells respond differently to drugs in 3D than 2D. Hence there has been a move towards performing drug assays in 3D spheroids. However, preparing spheroids is very time consuming. With Inventia Life Sciences, ACN is developing a 3D printing approach to provide a high throughput way of preparing 3D cell spheroids. Such a technology will provide cell biologists and nanomedicine researchers with rapid ways of testing the efficacy of new nanomedicines.
A home-use biosensor for glycosylated haemoglobin (HbA1c)
In collaboration with AgaMatrix Inc.
The percentage of glycosylated haemoglobin (HbA1c) in the blood of a diabetics patient is an important 3 month biomarker of the effectiveness of the blood glucose management regime of the patient. A 1% drop in HbA1c levels can result is a 20% drop in the chronic effect of diabetes. To measure the percentage of HbA1c requires a sensor that can detect both the levels of HbA1c and the levels of haemoglobin. ACN has developed a patented electrochemical immunosensor technology that is the first electrochemical immunosensor that can operate in whole blood. With ACN's industrial partners the ACN is developing the first ever HbA1c biosensor that can interface with existing blood glucose meters.
MicroRNA detection using magnetic nanoparticles
MicroRNA (miRNA) is small pieces of RNA, about 20 base pairs long, that have recently been discovered as important gene expression regulators within the body. From a diagnostics perspective they are particularly important new class of biomarker for disease diagnosis, including cancer, because the levels of different miRNA sequences changes with a pathology and because they are readily available because they circulate in the blood stream. The challenge is the levels of the miRNAs can range between from 10 fmol/L and 1.0 pmol/L and hence ultrasensitive diagnostic devices are required. This project uses the gold coated magnetic nanoparticle electrochemical sensor technology developed by the ACN which has been shown to be ultrasensitive but with very rapid response times. These new sensors are applied to miRNAs for the first time where the levels of miRNAs through different tissues as well as the blood will be determined such that a robust analytical method can be developed.
Nanopores for single molecule sensors
Diagnostic tools for early warning of a pathology typically must be able to detect concentrations of 1 fM or lower of a biomarker. The ultimate detection limit for a sensor is a single molecule. Although there are devices that can detect a single molecule they typically lack analytical utility due to slow response times. The ACN is addressing the challenge of rapidly responding single molecule sensors using nanopore sensors where magnetic nanoparticles bring the analyte to the pore. This new type of sensor would represent the ultimate diagnostic device.
Single molecule sensing using super-resolution light microscopy
Single molecule sensors that could detect many single molecule binding events simultaneously would then provide better quality, more analytically robust diagnostic devices that can overcome issues of interference. To do this requires the device to be able to detect single molecule events over a broad area. Until recently we have not had instrumentation to do this but the invention of super-resolution microscopy, and in particular stochastic microscopy, provides this capability but such tools have never been used for sensing. The ACN is making the first strides towards using these new tools for molecular counting for diagnostic devices by developing the first ever single molecule pull-down assays that do not require any wildtype cells.
Porous silicon photonic crystals for cell chips
Cell chips are invaluable for evaluating how cells respond to stimuli such as drugs and toxins in a high throughput manner. Traditionally cell chips are simply surfaces in which cells are immobilised in a well-controlled manner and then their response to stimuli is monitored using fluorescence microscopy. The ACN is developing surfaces that are not only platforms for cell immobilisation but also report on the response of the cells. This is achieved using porous silicon photonic crystals that are combined with enzyme responsive biogels. Immobilised cells that respond to the stimuli, it releases enzymes that degrade the enzyme responsive biogel and the photonic signature changes. The first generation of device detects protease activity released from immune cells. These devices are being developed for in vivo detection of protease activity and towards developing cell chips that can detect the response of arrays of single cells. Such devices are not only valuable tools for personalised medicine and nanotoxicology but also will provide a valuable tool for providing cell biologists with information on cell heterogeneity.
Capture and release of single rare cells
Rare cells circulating in the blood stream are of prime important in the establishment of metastatic cancers (so called circulating tumour cells or CTCs) and other pathologies. The enumeration of CTCs is of major interest for diagnostics. Most enumeration technologies involve the capture of cells on a surface. Furthermore, being able to studies these cells further in functional assays which requires their release from capture surfaces. ACN has developed technology that allows the electrochemical release of individual cells from anywhere on a surface upon which they are captured. This is a new capability that provided biomedical researchers with a valuable tool to study the heterogeneity in rare cells such as CTCs.
Novel light-activated materials for molecular tracking and biosensors
The main object of this work is developing functional systems that are controlled by light. This includes both redox protein systems that could be used for biosensors, novel approach for tracking the various component in nanoparticle assemblies and new dyes that could be used for cancer research and molecular imaging. Part of this work is also concerned with developing better polymersomes that include light-activated component for applications such as intra-cellular drug trafficking and release.
Design and development of novel microfluidic co-culture systems
Glial cells direct neurons in their early stages of development and regulate their normal firing activity. The communication between these two cell types plays a key role in their cellular functions. Conventional in vitro techniques are often inadequate to obtain enough information from this complex network. Recent advances in microfluidic technologies have opened doors for creating more realistic in vitro cell culture methods that mimic many aspects of the in vivo microenvironment such as cellular communication. In this project, we will develop a new microfluidic device for rapid patterning of cells into arbitrary substrates with an interlaced configuration for electrophysiological characterization of neuron-Schwann cell activity.
High throughput microfluidic systems for biomedical applications
Cell sorting is critical for many applications ranging from stem cell research to cancer therapy. Isolation and fractionation of cells using microfluidic platforms have been flourishing areas of development in recent years. The need for efficient and high-throughput cell enrichment, which is an essential preparatory step in many chemical and biological assays, has led to the recent development of numerous microscale separation techniques.
The proposed research is to develop a novel multiplexed microfluidic platform for ultra-high throughput (~ 1-1000 mL/min), label/clog-free separation of targeted cells (e.g., CTCs, MSCs, parasites and yeast) from various biological samples.
Fetal cell sorting using inertial microfluidics
Fetal cells from the maternal circulation have the potential to replace cells from amniotic fluid or chorionic villi in a diagnosis of common chromosomal aneuploidies; however, reliable markers for enrichment and identification are still missing. In this study, for the first time, we plan to demonstrate the usability of inertial microfluidics for ultra-fast, label-free isolation of circulating fetal cells found in maternal blood from 5 weeks gestation.
Isolation and characterization of CTCs using inertial microfluidics for early-stage breast cancer patients
The potential utility of circulating tumor cells (CTCs) to guide clinical care and understand the biology of metastasis has gained momentum over the past decade evidence by numerous publications and over 270 registered clinical trials. Yet, the clinical utility of CTCs has be hampered due to inherent limitation of conventional approaches for CTC isolation/identification and also scarcity and the lack of reliable markers to enrich these cells. We have recently developed a novel microfluidic system which can isolate and retrieve viable CTCs from blood based on size and deformability of cells, surmounting the shortcomings of traditional affinity-based separation techniques. The main aim of this project is to utilize this system for isolation and identification of CTCs from early-stage breast cancer patients and utilise them as a marker for early cancer diagnosis.
Cell-cycle sorting using spiral microfluidics
The ability to efficiently synchronize and select mammalian cells into different stages of their cell cycle is an important technique for the precise studies of various cellular properties, biological processes, and genetic mechanisms involved in cell cycle phase prior to division. Current chemical-based synchronization methods are unfavourable as these can disrupt cell physiology and metabolism. In this project, I am planning to develop a high-throughput microfluidic system for large-scale cell cycle synchronization suitable for industrial applications. By exploiting the relationship between cell size and its phase in the cell cycle, large numbers of synchronized cells can be obtained by size fractionation.