Autonomous capillary microfluidic system with embedded optics for improved troponin I cardiac biomarker detection

 Cardiovascular diseases are the most prevalent medical conditions affecting the modern world, reducing the quality of life for those affected and causing an ever increasing burden on clinical resources. Cardiac biomarkers are crucial in the diagnosis and management of patient outcomes. In that respect, such proteins are desirable to be measured at the point of care, overcoming the shortcomings of current instrumentation. We present a CO2 laser engraving technique for the rapid prototyping of a polymeric autonomous capillary system with embedded on-chip planar lenses and biosensing elements, the first step towards a fully miniaturised and integrated cardiac biosensing platform. The system has been applied to the detection of cardiac Troponin I, the gold standard biomarker for the diagnosis of acute myocardial infarction. The devised lab-on-a-chip device was demonstrated to have 24 pg/ml limit of detection, which is well within the minimum threshold for clinically applicable concentrations. Assays were completed within approximately 7–9 min. Initial results suggest that, given the portability, low power consumption and high sensitivity of the device, this technology could be developed further into point of care instrumentation useful in the diagnosis of various forms of cardiovascular diseases. 2014 Elsevier B.V. All rights reserved.

Design, characterization and application of a novel mono-layer pin-microvalve for microfluidic devices

Valves are one of the key components in microfluidic devices to control the fluid flow. In this paper we introduce a novel manual pin-valve which can operate in both analogue (partially close) and digital (on/off) states. We also demonstrate implementation of this pin-valve in a hydrodynamic flow focusing (HFF) device. © The Royal Society of Chemistry 2014.

A simple microfluidic chip design for fundamental bioseparation

A microchip pressure-driven liquid chromatographic system with a packed column has been designed and fabricated by using poly(dimethylsiloxane) (PDMS). The liquid chromatographic column was packed with mesoporous silica beads of Ia3d space group. Separation of dyes and biopolymers was carried out to verify the performance of the chip. A mixture of dyes (fluorescein and rhodamine B) and a biopolymer mixture (10 kDa Dextran and 66 kDa BSA) were separated and the fluorescence technique was employed to detect the movement of the molecules. Fluorescein molecule was a nonretained species and rhodamine B was attached onto silica surface when dye mixture in deionized water was injected into the microchannel. The retention times for dextran molecule and BSA molecule in biopolymer separation experiment were 45 s and 120 s, respectively. Retention factor was estimated to be 3.3 for dextran and 10.4 for BSA. The selectivity was 3.2 and resolution was 10.7. Good separation of dyes and biopolymers was achieved and the chip design was verified.

Microfluidic platforms for biomarker analysis

Biomarkers have been described as characteristics, most often molecular, that provide information about biological states, whether normal, pathological, or therapeutically modified. They hold great potential to assist diagnosis and prognosis, monitor disease, and assess therapeutic effectiveness. While a few biomarkers are routinely utilised clinically, these only reflect a very small percentage of all biomarkers discovered. Numerous factors contribute to the slow uptake of these new biomarkers, with challenges faced throughout the biomarker development pipeline. Microfluidics offers two important opportunities to the field of biomarkers: firstly, it can address some of these developmental obstacles, and secondly, it can provide the precise and complex platform required to bridge the gap between biomarker research and the biomarker-based analytical device market. Indeed, adoption of microfluidics has provided a new avenue for advancement, promoting clinical utilisation of both biomarkers and their analytical platforms. This review will discuss biomarkers and outline microfluidic platforms developed for biomarker analysis.

Microfluidic platforms for the investigation of intercellular signalling mechanisms

Intercellular signalling has been identified as a highly complex process, responsible for orchestrating many physiological functions. While conventional methods of investigation have been useful, their limitations are impeding further development. Microfluidics offers an opportunity to overcome some of these limitations. Most notably, microfluidic systems can emulate the in-vivo environments. Further, they enable exceptionally precise control of the microenvironment, allowing complex mechanisms to be selectively isolated and studied in detail. There has thus been a growing adoption of microfluidic platforms for investigation of cell signalling mechanisms. This review provides an overview of the different signalling mechanisms and discusses the methods used to study them, with a focus on the microfluidic devices developed for this purpose.

A parametric study of a monolithic microfluidic system for on-chip biomolecular separation

A microfabricated poly(dimethylsiloxane) (PDMS) chip containing channel filled with polymer monolith has been developed for on-chip biomolecule separation. Methacrylate monolithic polymers were prepared by photo-initiated polymerization within the channel to serve as a continuous stationary phase. The monolithic polymer was functionalized with a weak anion-exchange ligand, and key parameters affecting the binding characteristics of the system were investigated. The total binding capacity was unaffected by the flow rate of the mobile phase but varied significantly with changes in ionic strength and pH of the binding buffer. The binding capacity decreased with increasing buffer ionic strength, and this is due to the limited available binding sites for protein adsorption resulting from cationic shielding effect. Similarly, the binding capacity decreased with decreasing buffer pH towards the isoelectric point of the protein. A protein mixture, BSA and ovalbumin, was used to illustrate the capacity of the methacrylate-based microfluidic chip for rapid biomolecule separation.

Locked nucleic acid aptamer based microfluidic devices for capturing tumor cells

Design and fabrication of novel microfluidic devices for sensitive and specific capture of circulating tumor cells using locked nucleic acid modified aptamers and antibodies targeting EpCAM/Nucleolin expression. These devices also allow re-usability, on-chip characterization of multiple markers and release of viable captured cells for further culture and in vitro characterization for cancer diagnosis, prognosis and therapeutic planning.

Improved manufacturing quality and bonding of laser machined microfluidic systems

Laser micro-machining offers a versatile tool for the rapid manufacturing of polymeric microfluidics systems, with a typical turn-around-time in the order of minutes. However, the chaotic nature of the thermal evaporative ablation process can yield a significant number of defects in the surface of the manufactured microchannels, in the form of residual condensed material. In this work we have investigated the use of solvent evaporation by which to not only laminate bond the laser machined structures but to remove a significant number of the defect formed by the condensation of residual polymer. Results are presented of the surface profiling of the bonded channel structures and demonstrations of the bonding of the microchips to produce autonomous capillary microchannels.

Novel approach to trigger nanostructures in thermosets using competitive Hydrogen-Bonding-Induced Phase Separation (CHIPS)

A new route to prepare nanostructured thermosets by the utilization of intermolecular hydrogen-bonding interactions is demonstrated here. In this study, competitive hydrogen-bonding-induced microphase separation (CHIPS) in epoxy resin (ER) containing an amphiphilic block copolymer poly(ε-caprolactone)-block-poly(2-vinylpyridine) (PCL-b-P2VP) is investigated for the first time. The phase separation takes place due to the disparity in the hydrogen-bonding interactions in ER/P2VP and ER/PCL pairs leading to the formation of ordered nanostructures in the ER/block copolymer blends. SAXS and TEM results indicate that the hexagonally packed cylindrical morphology of neat PCL-b-P2VP block copolymer remains but becomes a core-shell structure at 10 wt % addition of ER, and changes to regular lamellae structures at 20-50 wt % then to disordered lamellae with 60 wt % ER. Wormlike structures are obtained in the blends with 70 wt % ER, followed by a completely homogeneous phase of ER/P2VP and ER/PCL. The formation of nanostructures and changes in morphologies depend on the relative strength of hydrogen-bonding interactions between each component block copolymer and the homopolymer. This versatile method to develop nanostructured thermosets, involving competitive hydrogen-bonding interactions, could be used for the fabrication of hierarchical and functional materials.

Multicomponent materials from machining chips compacted by equal-channel angular pressing

Al and Mg machining chip blends were compacted by equal-channel angular pressing with back pressure. By varying the weight fraction of the constituent materials, temperature and processing route, as well as employing subsequent heat treatment, the microstructure and the mechanical properties of the compact were varied. The width of the interdiffusion zone and the formation of intermetallic phases near the interfaces between the two metals were studied by energy-dispersive X-ray spectroscopy and nanoindentation. It was shown that substantial improvement of mechanical properties, such as an increase of strength, strain-hardening capability and ductility, can be obtained. This is achieved by changing the processing parameters of equal-channel angular pressing and the annealing temperature, as well as by optimising the weight fraction of the constituent metals. © 2013 Springer Science+Business Media New York.

A Modular design framework for Lab-On-a-Chips

This research discusses the modular design framework for designing Lab-On-a-Chip (LoC) devices. This work will help researchers to be able to focus on their research strengths, without needing to learn details of LoCs design, and they can reuse existing LoC designs.

Exercise and skeletal muscle gene expression

1. Skeletal muscle is a complex and heterogenous tissue capable of remarkable adaptation in response to exercise training. The role of gene transcription, as an initial target to control protein synthesis, is poorly understood.
2. Mature myofibres contain several hundred nuclei, all of which maintain transcriptional competency, although the localized responsiveness of nuclei is not well known. Myofibres are capable of hypertrophy. These processes require the activation and myogenic differentiation of mononuclear satellite cells that fuse with the enlarging or repairing myofibre.
3. A single bout of exercise in human subjects is capable of activating the expression of many diverse groups of genes.
4. The impact of repeated exercise bouts, typical of exercise training, on gene expression has yet to receive systematic investigation.
5. The molecular programme elicited by resistance exercise and endurance exercise differs markedly. Muscular hypertrophy following resistance exercise is dependent on the activation of satellite cells and their subsequent myogenic maturation. Endurance exercise requires the simultaneous activation of mitochondrial and nuclear genes to enable mitochondrial biogenesis.
6. Future analysis of the regulation of genes by exercise may combine high-throughput technologies, such as gene-chips, enabling the rapid detection and analysis of changes in the expression of many thousands of genes.

Self-crimping bicomponent nanofibres electrospun from polyacrylonitrile and elastomeric polyurethane

Two polymer solutions were brought together via a microfluidic device and subjected to an electrospinning process. The two polymer solutions flowed into the microfluidic channel side-by-side with very little intermixing due to their laminar nature. High speed stretching of the polymer solutions resulted in side-by-side bicomponent fibres. The electrospun nanofibres exhibited an extremely high propensity to self-crimp when an elastomeric polymer (polyurethane) and a normal polymer (polyacrylonitrile PAN) were involved in the electrospinning process. The formation of self-crimping fibre morphology was attributed to the differential shrinkage of the two polymers.

Food and activity in out of school hours care in Victoria

Objective: To describe characteristics of the Victorian out of school hours care (OSHC) sector to assess its potential role in promoting healthy lifestyles to children and their families.

Design: Written questionnaires were sent to 1100 Victorian OSHC programs to collect information about the services, foods and activities offered to children, the training and resources utilised by staff and the type of information sent home to parents/guardians.

Subjects: A total of 426 Victorian OSHC coordinators completed questionnaires in the present descriptive study (39% response rate).

Setting: Out of school hours care provides care for 5–12 years olds before school, after school and/or during school holidays.

Results: Over 80% of coordinators reported offering fruit, breads, cereals, and milk and dairy products. One-third offer vegetables as part of meals or snacks. One-third reported offering cakes, biscuits and/or slices, and chips and/or pastries. About 17% reported offering water, whereas 24% reported offering cordial/soft drinks and fruit juice. Cooking was offered as an after-school activity by about half of those surveyed. Active games were common (62%) as were indoor active games and sports (36%). Sedentary activities were also commonplace (37–51%). Only about 30% of OSHC coordinators had participated in nutrition and/or physical activity training in the previous two years. Few OSHC programs sent home health information to parents/guardians.

Conclusion and application: Opportunities exist to help Victorian OSHC programs with nutrition and physical activity information, resources and training. Although the findings of the present study are specific to Victoria, they highlight the potential role of the growing OSHC sector to help improve the health of Australian children.