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Institute for Life SciencesOur research

Microfluidics

Microfluidics, the transport of small volumes, can be used to analyse molecules and single cells with extreme precision, offering vastly improved analytical performance. Integration with electronics and sensors enables complete assay automation for real-time decision-making at the point of care. 

Image supplied by Prof Hywel Morgan
Microfluidic Device

The Institute for Life Sciences Centre for Hybrid Biodevices unites expertise in Microfluidics with leading expertise in Biology and Medicine for fundamental research and also to collaborate with industry.

This theme incorporates research in the following areas:

i) Point of Care Analytics:

Development of integrated Lab on Chip sample processing and diagnostic systems, including hand-held EWOD (electrowetting on dielectric) systems, printed circuit board technology, nanowire sensing and droplet sampling for monitoring during surgery.

ii) Single Cell Analysis:

Microfluidics is ideally suited for single cell measurements, with application in cancer immunology, stem cell biology, receptor signalling and platelet biology.

iii) Tissue Models:

Ex vivo tissue models can be prepared and analysed using microfluidics. Research spans the lung on a chip, neurocircuit and biomimetic blood vessel projects.

iv) Neuroscience:

Automated systems for high throughput electrophysiological recordings from model organisms such as the worm C. elegans.

v) Environmental Monitoring:

Multi-parametric chemical and biological sensors can be deployed to provide a detailed understanding of our oceans.

For more information about the Microfluidic theme please contact the theme leads below:

Related Staff Member

Related Staff Member

Related Staff Member

The Institute funds a cohort of interdisciplinary PhD studentships each year. Current postgraduate students in this field include:

William Anderson

William Anderson

A microfluidic droplet sorter based on surface-enhanced Raman spectroscopy.

Faith Bateman

Faith Bateman

Design of a microfluidic device that is capable of viewing immune interactions at the single-cell level

Marios Stavrou

Marios Stavrou

Time Machines: Microfluidic investigation of epidermal growth factor receptor signal transduction mechanisms.

Cara Vallance

Cara Vallance

Integration of Microfluidic Cell Culture with NMR Spectroscopy for Correlation Metabolomics.

Key Publications

Image supplied by Dr Xunli Zhang
Therapeutic Emoblisation

i) Point of Care Analytics:

Therapeutic Biomicrofluidics - Dr Xunli Zhang

Our research aims to develop microfluidic technology which can potentially provide platforms for in-vitro characterisation and evaluation of clinical procedures involving micro scale body fluids such as blood and urine. Currently, the preclinical development and performance assessment of those procedures have been carried out predominantly through animal models, where unmet challenges include technical limitations, economic issues, and regulatory and ethical considerations. Biomimetic microfluidics-based platforms allow us to detect the performance of fluids in real time with high spatial resolution, and enable greater control over the experimental variables than animal testing does in terms of definition of boundary conditions, mimicking physio-pathological fluidic environments, and direct access to a wide range of physical parameters of interest, ultimately, leading to the development of an alternative method to animal tests.  Therapeutic embolisation is a clinical procedure in which foreign material (i.e. embolic agent in the form of micro-sized beads) is introduced into a blood vessel in order to selectively reduce or completely arrest the blood flow to tumours. By loading anticancer drugs to the embolic beads it enables chemoembolisation where drugs are directly administered from the embolic agents, thus synergistically combining the therapeutic effect of the drug with the hypoxic action of embolisation.

We have developed an artificial model to mimic the blood vessel network using microfluidic technologies. It allows precise control to create and finely adjust the fluidic microenvironment in a biomimetic format. In addition, coupling with microscope-based imaging techniques provides a platform for the detection and quantification of behaviour of both microparticles and fluid in real time.

Image supplied by Dr Jonathan West
Cell-Driven Micromixing

ii) Single Cell Analysis:

TIME MACHINES: Temporally Resolved Signal Transduction Mechanics - Marios Stavrou and Dr Jonathan West

The interface between the cell surface and its microenvironment represents the communication front for signal transduction, information processing and the emergent behaviour of the biological system. The mechanics of receptor-mediated signal transduction remain poorly understood due to an absence of techniques with sufficient temporal resolution. To address this, a whole cell quenched flow analysis platform has been developed to resolve cell surface processes with millisecond resolution. The platform incorporates a high-speed microfluidic processor for switching single cells between biochemical microenvironments to initiate, incubate and then preserve reaction intermediates. In collaboration with Prof. Donna Davies and Ben MacArthur, the technology is being applied to elucidate the sequence of events underpinning the activation of the epidermal growth factor receptor (EGFR), a receptor essential for normal growth and development but also involved in cancer. 

 

FREE-FLOW: Surveying Single Platelet Functionality – Maaike ‘Sybil’ Jongen and Dr Jonathan West

 Platelets are sub-cellular homeostatic control agents that act as dispersed sentinels for the co-ordinated identification and repair of vascular injury. Imbalance in this tightly regulated system can, on the one hand, lead to excessive bleeding or, on the other, lead to pathologic thrombus formation and the risk of stroke or heart attacks. This project is run in collaboration with Dr Nicola Englyst and Dr Ben MacArthur, and involves the application of high throughput microfluidic techniques with statistical methods to investigate the functional capacity of single platelets and provide a systems-level understanding of the clotting process in health and in disease.

 

An electronic-based ELISA combined with microfluidics - Dr Themis Prodromakis

This project’s aim is to develop a low-cost real-time protein detection device to continuously monitor cytokines during in-vitro culture that could eventually expand in clinical practice. We are currently exploiting discrete electronic components as chemical sensors that are compatible with unique microfluidic chips for minimising the overall cost of the device in combination with small size enzyme-linked immunosorbent assay (ELISA) chambers that minimise antibody requirements. This project leverages well established manufacturing techniques, currently employed in fabricating printed-circuit boards (PCBs), for effortlessly rendering bespoke functionalised electrodes coupled with μm-scale fluidic channels/chambers.

Image supplied by Dr Maurits de Planque
Cell Arraying Platforms

iii) Microfluidic Tissue Models:

Cell arraying platforms - Dr Maurits de Planque

White blood cells play a central role in the defence against bacterial, viral and fungal pathogens. As there is only one white blood cell for every 1000 red blood cells, white blood cell isolation is not trivial. Filtering, differential centrifugation, or selective lysis of red blood cells all have disadvantages and require a relatively large blood volume. We have developed a microfluidic system with hydrodynamic cell traps that selectively capture white blood cells from a whole blood sample. The traps and therefore the immobilized cells are optically accessible, presenting an array of white blood cells that can be studied, at a sub-cellular level, with conventional biochemical labelling methods. Whilst cell arrays are of general interest for cell population heterogeneity studies, e.g. different responses to external stimuli, our initial focus is on establishing nanoparticle association and uptake for different white blood cell types, identified by antibody labelling of distinct membrane receptors.

Portable droplet microfluidics for continuous monitoring and diagnostics - Dr Xize Niu

Continuous measurement of biomolecule/drug concentrations directly from tissue (or other body) fluids offers the exciting possibility of understanding physiological or pathological processes, recording responses to stimuli, drug metabolism, and even developing new therapies that use biomarker levels to guide treatment in real time. However, such measurement is challenging - the fluids are complex mixtures, the volumes can be very small, and detection methods are limited. In this project we propose to tackle this challenge through the development of an enabling portable sensor device. The device combines microdialysis and droplet microfluidic techniques, will perform assays and measurements in situ, and communicate wirelessly to the user. We envisage this novel technology will revolutionize the current practices of sampling and chemical sensing, and find broad applications in disease diagnostics and monitoring, drug development, organ transplantation and the other areas.

Neurotraffic: Material Propagation in Neuronal Circuits – Prutha Patel, Grace Hallinan, Dr Jo Bailey, Dr Jonathan West and Dr Katrin Deinhardt 

Material trafficking within neuronal circuits underlies a variety of diseases. The recent prion hypothesis of neurodegenerative diseases poses that protein aggregates found for example in Alzheimer’s and Parkinson’s diseases may also propagate in this way. This research involves the development of next generation microfluidic analysis platforms for the construction of precisely defined neuronal circuits and connectivity. These ex vivo neuronal circuits will be used to unravel the mechanisms involved in the propagation of hyperphosphorylated tau along outgrowths and across synaptic junctions, and also as a means to investigate long-range BDNF-mediated signalling.

Image supplied by Prof Hywel Morgan
NeuroChip

iv) Neuroscience:

NeuroChip - Prof Lindy Holden-Dye & Prof Hywel Morgan

We have developed a new microfluidic device, NeuroChip, that can sequentially trap worms and record neural electrophysiological signal combined with the capability to administer drug solutions while recording these signals.  Genetic and chemical biology screens of a minute worm called C. elegans have been of enormous benefit in providing fundamental insight into neural function and the effect of neuroactive drugs. Recently the exploitation of microfluidic devices has added greater power to this experimental approach providing more discrete and higher throughput phenotypic analysis of neural systems. We a developing a new microfluidic device, NeuroChip, that can sequentially trap worms and record neural electrophysiological signal combined with the capability to administer drug solutions while recording these signals. With the integration of micro-valves and embedded electrodes, a new tool for consistent, high-quality and high-throughput neurogenetic and neuropharmacological analysis of worms can be achieved. We are currently modifying the chip for electrophysiological analysis of small nematodes and for high throughput compound screening.

Hu C, Kearn J, Urwin P, Lilley C, O' Connor V, Holden-Dye L, Morgan H. StyletChip: a microfluidic device for recording host invasion behaviour and feeding of plant parasitic nematodes. Lab Chip. 2014 Jul 21;14(14):2447-55. doi: 10.1039/c4lc00292j.
Hu C, Dillon J, Kearn J, Murray C, O'Connor V, Holden-Dye L, Morgan H.NeuroChip: a microfluidic electrophysiological device for genetic and chemical biology screening of Caenorhabditis elegans adult and larvae. PLoS One. 2013 May 22;8(5):e64297. doi: 10.1371/journal.pone.0064297. Print 2013

 

NEUROTRAFFIC: Propagation in Neuronal Circuits - Dr Jonathan West

Material trafficking within neuronal circuits underlies a variety of diseases. The recent prion hypothesis of neurodegenerative diseases poses that protein aggregates found for example in Alzheimer’s and Parkinson’s diseases may also propagate in this way. This research involves the use of advanced microfluidic analysis platforms for the preparation of well defined neuronal [1,2,3]. These minimalistic ex vivo constructs will be used to unravel the mechanisms involved in the propagation of hyperphosphorylated tau and long-range BNDF-mediated signalling.

N.D. Dinh et al, Microfluidic construction of minimalistic neuronal co-cultures, Lab on a Chip, 2013, 13(7), 1402–1412.
N.D. Dinh et al, Preparation of neuronal co-cultures with single cell precision, Journal of Visualized Experiments, 2014, 87, doi: 10.3791/51389

 

v) Environmental Monitoring:

 

List of related projects to
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