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The University of Southampton
Global Network for Anti-Microbial Resistance and Infection Prevention

Novel engineering approach to tackle tuberculosis

Tuberculosis (TB) remains a major global pathogen, killing more individuals than any other bacterial disease worldwide.The Tuberculosis research group in Medicine and Dr Zhang's group in Engineering collaborated through NAMRIP to address the challenge of drug-resistant tuberculosis by combining advanced cell culture methodology and microfluidics.

The goal of this pump priming project was to develop a novel microfluidic platform integrating the recently developed microsphere-based 3-dimensional (3-D) cell culture model of human TB infection, allowing high throughput screening of the microenvironment surrounding the 3-D cell culture model with precise fluidic control.

Microfluidic system that has been developed
Microfluidic system that has been developed

The image shows the developed microfluidic system in a 24-well tissue culture plate format with 2 input channels and one exit channel for each well. This allowed drug concentration to be varied over time and mimic changes that occur in a patient after taking mediciation.

During system development, an additional feature was designed where a basal mirror was added to the microfluidic device which significantly enhanced the detection of the luminescence readout from the cells.

Using the microfluidic system developed, modelling of antibiotic concentration profiles was successfully achieved, as a proof-of-concept for high throughput testing.



Future of this research

The pump priming project provided the opportunity to synergise Dr Zhangs’s microfluidic and manufacturing expertise with Professor Elkington's cell culture system - the sum of the 2 parts being greater than the individuals.

Integration of biological and physical sciences has allowed more accurate modelling of conditions in patients and demonstrated that antibiotic killing reflects conditions in vivo. This system could be applied to a wide range of pathogens.

The project has developed in Global-NAMRIP into a collaboration with the Africa Health Research Institute (AHRI), Durban, South Africa, in a project which  links the 3-D modelling and microfluidic work at Southampton with the AHRI. This new research project is funded by a Medical Research Council Global Challenge Research Fund Foundation Award. The team are also collaborating with the Indian Institute of Technology (IIT) Kharagpur, India.

Project Team: Dr Xunli Zhang, Faculty of Engineering and the Environment, Professor Paul Elkington, Faculty of Medicine, Dr R Zmijan and Dr M Bielecka.

This project was funded by the EPSRC's Network for Antimicrobial Action, 'Bridging the Gap' programme, EP/M027260/1 (Round 1 of Pump Priming).


Outputs to date: Bielecka MK, Tezera LB, Zmijan R, Drobniewski F, Zhang X, Jayasinghe S, Elkington P. 2017. A bioengineered three-dimensional cell culture platform integrated with microfluidics to address antimicrobial resistance in tuberculosis. mBio 8:e02073-16.

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