Find out more information about our research projects below
Human airways on a chip
The study of human airways and the barrier function is essential to achieve a better understanding of lung diseases such asthma and COPD. This project replaces animal models with a microfluidic device capable of long-term cell culture. The chips provide continuous flow of media to the 3-D cell constructs and continuously monitor epithelial barrier function using an integrated sensor. Cells are grown at the air-liquid interface and can easily be challenged with allergens and viruses. The technology also provides continuous micro sampling of the extra cellular environment so that inflammatory markers can be measured in real time. This platform will further our understanding of asthma and provide a platform for compound screening for new medicines.
Hywel Morgan, Donna Davies, Emily Swindle
Microfluidic Devices for the Temporal Resolution of T Lymphocyte Competition
In the human body there could be multiple immune responses to different antigens at the same time. However, in general only one response dominates – this is called immunodominance and the cause is unknown. Studies to date have investigated the phenomenon using bulk cell populations, but this will mask any heterogeneity within the population. This project will deliver a microfluidic chip capable of trapping thousands of pairs of single cells and then bringing them into contact for a predefined period of time. The device measures single cell response via Calcium signalling and also single cell protein expression.
Hywel Morgan and Tim Elliott
Human reproduction is described as crucial but relatively inefficient. This is primarily due to peri-implantation pregnancy loss and first trimester miscarriage. Very little is known about the environment within the uterus and how it alters through the menstrual cycle. This reflects the lack of clinically relevant diagnostic approaches for interrogating uterine functions. If these issues are to be addressed, a greater understanding of intra-uterine environment and what constitutes the receptive endometrium can be required. This project aims to develop an implantable multi-parameter sensing device for real-time monitoring of the intra-uterine environment. The batteryless implantable smart sensor will sense temperature, dissolved oxygen concentration (DO) and pH, parameters shown to influence early embryo development. A wearable receiver wirelessly powers the sensor and captures the sensor data. A prototype system has been tested on pigs and rabbits and we will shortly be undergoing a human trial.
Microfluidic blood count
A full blood count is one of the most commonly ordered clinical tests with over 300 million tests per year ordered in the US alone. A test involves identifying and counting the different types of blood cells and is currently done with large and expensive equipment in a centralised laboratory. We are developing a miniature Point of Care test that requires only a fingerprick of blood and provides accurate results in a few minutes. Cell analysis is performed using microfluidic impedance cytometry (MIC) which measures the dielectric properties of cells as they flow between micro-electrodes in a microfluidic chip. The device includes microfluidic sample preparation that performs accurate sample metering. The system also includes micro-optics to measure fluorescent antibody labelled cells, extending the detection capability beyond the standard test. For instance for counting CD4 T-lymphocytes in blood, a commonly used test to diagnose and monitor HIV/AIDs.
Hywel Morgan and Daniel Spencer
Low cost diagnostics for parasite infection.
There is a need for new approaches to diagnose parasite infection that replaces the laborious methods currently used that require sample staining and expert identification under high optical magnification. Ideally, a system should be much simpler to enable use by a non-expert and should be more sensitive and accurate for earlier detection. Malaria is a significant global health problem where rapid diagnostics and early intervention could save lives. The challenge is to detect as few as 10 parasite infected red blood cells within millions of healthy cells. It is known that parasite infected cells differ in shape and stiffness and we have recently identified differences in their dielectric properties. This project is developing an analysis platform that exploits a combination of these biophysical parameters in order to rapidly identify small numbers of parasites in a blood sample at the point of care.
Hywel Morgan, Daniel Spencer and Carlos Honrado
In collaboration under the framework of the LAPASO project with Lisa Ranford-Cartwright, University of Glasgow and Jonas Tegenfeldt, Lund University .
Label free stem cell characterisation and sorting
Skeletal stem cells (SSC) are a sub-population of mesenchymal stem cells, found in bone marrow and have shown osteogenic, chondrogenic and adipogenic differentiation potential. However, efficient isolation of these cells remains a challenge because they are scarce and lack a specific biochemical marker. Microfluidics devices could provide novel solutions for cell separation based on bio-physical features of single cells, for example stiffness and dielectric properties. We have shown that surrogate cells (MG-63) differ sufficiently in size and mechanical stiffness or deformability to indicate that these cells can be separated from leuckocytes using techniques such as Deterministic Lateral Displacement (DLD) arrays.
Hywel Morgan, Richard Oreffo, Daniel Spencer and Miguel Xavier
In collaboration under the framework of the LAPASO project with Jochen Guck, Technische Universität Dresden and Jonas Tegenfeldt, Lund University
Droplet interfaced in situ compartmentalization after isoelectric focusing separation with a Slipchip
Isoelectric focusing (IEF) is a widely used technique for separating protein according to charge. Small sample analysis requires microscale IEF which typically uses capillaries or microfluidic chips. However, there remains a significant challenge to collect the separated sample fractions for further downstream analysis. We have used the “SlipChip” platform for in situ compartmentalization after IEF separation producing discrete sample droplets containing the separated proteins of interest.
Xize Niu and Hywel Morgan.
Measurement of water parameters is central to the management, security and prediction of water resource availability and use. Hence, there is strong demand for high accuracy and reliable autonomous sensors to instrument the aquatic environment. We have developed a deployable wet chemical sensor technology based on the use of microfluidic chips with integrated optical analysis. These devices offer rapid and multiplexed measurement of nutrients and other chemistries with high precision and accuracy, and can operate continuously at a depth of 2000m for many months at a time.
Hywel Morgan in collaboration with Dr. Matt Mowlem, NOC Southampton
Label-free biosensors based on nanowire transistors offer the possibility of an integrated all-electronic biosensing platform. These biosensors are often produced using a complicated SOI CMOS process with advanced lithography to define nanowires. We are developing a simple process that uses thin film technology with in-situ doping and low doped polysilicon film contacts. The TFT sensors have excellent near Nernstian pH response and stability. They behave similarly to SOI devices and can be used to measure protein binding in low-ionic electrolytes.
Hywel Morgan, Peter Ashburn, Maurits de Planque and Harold Chong
In collaboration with Sharp Labs Europe, Oxford Instruments Plasma Technology.
Digital Microfluidics (In collaboration with Sharp Labs Europe)
Digital Microfluidics (DMF) is a fluid-handling method for manipulating small nL droplets using arrays of microelectrodes, built using the same technology as mobile phone screens. Many diagnostic tests involve numerous fluid handling steps including dispensing, metering, mixing and washing, all of which can be accomplished using a fully automated and programmable DMF platform. The principle is based on electro-wetting on dielectric (EWOD) where electrodes coated with insulator can control the shape of a aqueous droplet. In collaboration with Sharp Labs Europe we are using very large arrays of electrodes that use Active Matrix technology, manufactured using Thin Film Transistor (TFT) technology. The devices are fully programmable and have integrated impedance droplet sensing enabling real time droplet position and volume measurement. Current work is exploring the use of these in multiplexed diagnostics and for parallel processing of large numbers of droplets containing single cells.
In collaboration with Sharp Labs Europe
Parallel electrophysiology of ion channels with lipid bilayer membranes (BLMs)
More than 50% of drugs target membrane proteins and their characterisation in their natural environment within a membrane is important. Artificial bilayer lipid membranes provide ideal platforms for protein characterisation but suffer from limited experimental throughput and lifetime. We have developed an integrated system that enables simultaneous electrophysiological recording from multiple bilayers. The system includes dedicated miniature electronic amplifiers (ASICs) and bilayers are made within disposable glass microfluidic chips. We have used these devices to measure drug interaction with ion channels (IC50). The long term goal is to characterise Na+ channel activity and the interaction with drugs.
Hywel Morgan and Maurits de Planque
Collaboration with Prof Bonnie Wallace, Birkbeck College, London and Prof Marco Tartagni, University of Bologna