Implantable Biosensors for Monitoring of Neuroinflammation

Lead Research Organisation: University of Cambridge
Department Name: Engineering

Abstract

Neuroinflammation plays an important role in the onset and progression of many neurodegenerative diseases, including Multiple Sclerosis, Alzheimer's and Parkinson's diseases. Recent research has uncovered a link between the presence of certain metabolites in cerebrospinal fluid (CSF) and neuroinflammation. Pro-inflammatory macrophages were shown to cause breaks in the tricarboxylic acid cycle leading to altered levels of succinate, itaconate and fumarate. Point-of-care testing for these biomarkers offers an opportunity to screen and diagnose such neurological diseases and monitor their progression.

Currently, the state-of-the-art biosensors for metabolite detection include microarray technologies, mass spectroscopy and Forster Resonance Energy Transfer microscopy. These are able to measure multiple biomarkers but lack the ability to perform real-time monitoring of animal models in-vivo and can have problems with sensitivity for low concentration biomarkers. This creates a need for new technologies which are able to perform point-of-care testing with low limits of detection and high sensitivity.

Electrochemical biosensors are a simple, low cost technology providing fast and highly sensitive analysis for specific target analytes. Implantable biosensor technologies enable the in-vivo electrochemical monitoring of biomarkers in real-time. This project proposes to develop a novel implantable biosensor which can monitor levels of these key metabolites in real-time and output recordable data.

The overall aim of the project is to develop and validate new ways and electrochemical technologies to monitor biomarkers of neuroinflammation in-situ. This would develop the potential for real-time point-of-care screening, early diagnosis, and monitoring of neurological diseases. In order to achieve this aim we devise two key objectives: (1) Development of biosensors capable of detecting neuroinflammation biomarkers in CSF. (2) Validation of the usability of the developed sensors through in-vivo implantation in a murine animal models for continuous monitoring.

This approach is broken down into three main stages. Firstly, we will design the biosensor: identifying suitable molecular mechanisms of the metabolite for measurement, and designing, developing and characterising a novel electrochemical biosensor with suitable capabilities and specifications. In-vitro testing in solution and cell culture media, and ex-vivo testing of cerebrospinal fluid will validate the performance of our developed biosensor technologies and inform optimisations of the devices. Finally, the developed sensors will be demonstrated through implantation in murine models for real-time continuous monitoring with results being validated through comparison with ex-vivo and microdialysis experiments.

Research will primarily be carried out in Dr Occhipinti's group, for all design, device development and characterisation experimental tasks, with access to advanced fabrication and characterisation facilities available in the Cambridge Graphene Centre and the Nanoscience Centre. The preclinical work will be developed in Dr Pluchino's lab in the Department of Clinical Neurosciences, who carry out translational research specialised in regenerative neuroimmunology.

This project is multidisciplinary and covers a number of EPSRC's research themes including engineering, physical sciences and healthcare technologies with research areas such as clinical technologies, sensors and instrumentations, and microelectronic device technology being explored.

The development and demonstration of a suitable biosensor will provide a step forward in the understanding and monitoring of neurodegenerative diseases.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/S023046/1 01/10/2019 31/03/2028
2262191 Studentship EP/S023046/1 01/10/2019 30/09/2023 Dafydd Ravenscroft