Joseph van Batenburg-Sherwood A new approach to active on-chip microfluidic pressure measurement Lab based Biomechanics and mechanobiology,Biomedical sensing diagnostics and imaging Measuring pressure in microchannels is tricky!A number of systems use on-chip strain gauge based pressure sensors, but fabrication of these has fundamental limitations. For example, it requires each channel to be fabricated with electrical connections to the pressure sensors that require calibration. When using biological fluids or cells, this is impractical. Furthermore, for complex structures or systems with incorporated hydrogels, this approach is not possible. Another option is to create a side branch in the channel and connect a pressure sensor to passively measure the pressure at the location of interest. The problem with this is that the unavoidable compliance in the system means that making the measurement will modify the flow. In summary all existing methods are too complex/impractical or too inaccurate. This project offers the opportunity to resolve this issue for the first time using an active pressure measurement approach. The idea is based on the ‘servo-null technique’ and involves applying a controlled pressure to a side branch until there is no movement between the fluid and main channel. Optical methods will be used to track particles or a fluid interface to control the movement of the fluid in the side branch. This new and exciting design project will incorporate computer-aided design, microfabrication, image processing, control algorithms, simple electronics and programming, flow control and measurement systems and data analysis.Please get in touch if you have any questions (
Joseph van Batenburg-Sherwood Designing microfluidic systems for characterisation of blood mechanical properties (up to 3 projects) Lab based Biomechanics and mechanobiology,Biomedical sensing diagnostics and imaging,Medical devices Blood leaving the heart flows through a branching network, reaching microvessels smaller than a hair in order to deliver oxygen to all cells in the body. In a number of diseases, such as diabetes and malaria, the microvessels do not get enough blood or leak, with consequences such as blindness, liver disease and even death. Proper function of microvessels is dependent on the blood flowing in them. Blood is made up of approximately equal portions of plasma and red blood cells. These specialist cells are highly deformable so that they can fit through capillaries and reversibly aggregate in regions of low shear stress. Together these behaviours change how blood flows, and in turn the microvessel function. Red blood cells are altered in patients with diseases such as diabetes. The cells are i) less deformable, ii) aggregate more, and correspondingly have iii) elevated viscosity with different shear thinning behaviour. For lab research, we need to be able to rapidly characterise these properties to identify their relationship with flow behaviour measured in our state-of-the-art blood micro-particle image velocimetry system. For the clinic, existing tools to measure these properties are very limited, and better monitoring of them could present new ways for clinicians to diagnose disease and predict disease progression. Due to the beautiful complexity of each of these properties, they are each worthy of a focussed project. Each project will therefore focus on RBC deformability, RBC aggregation or blood viscosity, and carry out a full design project on the device. This involves - determining design specifications- reviewing existing devices- producing possible design concepts - prototyping- testing with blood samples- evaluating for sensitivity and repeatabilityPlease get in touch if you have any questions (
Joseph van Batenburg-Sherwood Experimentally investigating the interactions between red blood cells and endothelial cells in disease (up to 2 projects) Lab based Biomechanics and mechanobiology Microvessels, smaller than a hair, are embedded in all living tissues to deliver nutrients and exchange gases. The regulation of microvascular blood flow must be tightly controlled and dysregulation is associated numerous diseases, such as diabetes. A major mechanism of regulation involves endothelial cells (ECs) that line all blood vessels and sense shear stresses from the flowing blood.  ECs then release bioactive compounds that dilate or constrict the vessel to control blood flow. While much research is focused on how ECs are affected by disease, less attention has been paid to how the blood itself changes. Clinical studies have reported the red blood cells (RBCs) of patients with diseases are different, for example they can be less deformable or aggregate more readily. We are interested in understanding how these changes to the blood can affect endothelial cell responses and thus disease progression.We have developed two models ‘blood-vessel-on-a-chip’ models, one in PDMS (easy to use and highly repeatable) and one in a collagen gel (more realistic but harder to use). In both, we can grow endothelial cells and investigate how they respond to the shear stress applied by normal and diseased blood samples using immunofluorescence. Both models are currently straight channels, and this is a limitation as the really interesting dynamics occur at microvascular bifurcations. In this project, the aim will be to develop a model of a microvascular bifurcation. This could be done using microfabrication methods or bioprinting (which can both be done in the department and/or with collaborators in medicine). The developed model can then be used to  study both the flow of blood and the response of endothelial cells to that flow. The project would involve aspects of experimental design, cell culture, immunofluorescence microscopy, fluids dynamics measurements and data analysis. Please get in touch if you have any questions (
Joseph van Batenburg-Sherwood Microfluidic systems for high-throughput screening of therapeutic drugs Lab based Biomechanics and mechanobiology,Biomedical sensing diagnostics and imaging,Medical devices Glaucoma is a leading cause of irreversible blindness and is caused by failure of the mechanisms that regulate the pressure in the eye. This pressure is generated and controlled by the flow of aqueous humour across a layer of specialised endothelial cells. The hydraulic conductivity of these cells decreases in glaucoma, and while the reasons for this aren’t fully understood, lowering the pressure by increasing the conductivity can protect patients from further loss of vision. However, few such treatments exist. We are developing in vitro microfluidic systems to accurately measure the hydraulic conductivity of endothelial cell layers that could be used to screen for compounds that increase conductivity without damaging the cells. Our novel approach uses velocity measurement of microparticles or bubbles to calculate flow rate and hence conductivity at various pressures.This project would involve developing and optimising this approach through design, simulation and experimentation. Techniques involved would include microfabrication, cell culture, fluid dynamics measurements and data analysis     Please get in touch if you have any questions (