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NC3Rs: National Centre for the Replacement Refinement & Reduction of Animals in Research
PhD Studentship

Developing microfluidic systems for high throughput studies of functional neuronal networks

A pink eppendorf rack

At a glance

Completed
Award date
September 2014
Grant amount
£90,000
Principal investigator
Dr Michele Zagnoni

Co-investigator(s)

Institute
University of Strathclyde

R

  • Replacement
Read the abstract
View the grant profile on GtR

Overview

Aims

This project aims to develop new microfluidic systems for neuronal culture that makes it possible to take simultaneous optical and electrical recordings of cellular activity.  Applications to drug screening, gene function and neurotoxicity will reduce the need for animal studies in these areas.

Background

Disorders of the central nervous system (CNS) have a severe impact on society, especially with an ageing population. Technological advances can drive forward understanding of how neuronal function and communication is altered in CNS disorders. In vitro methods have been valuable research tools for studying the function of neurons, but conventional techniques do not allow the parameters that influence cellular activity and communication to be controlled. Microfluidic technology could provide a viable solution to these problems because it can give researchers greater control over the formation of simplified neuronal networks that mimic conditions in animals.

Research details and methods

The aim of this project is to develop novel and high throughput microfluidic systems for advanced patterning of neuronal cultures. These will allow simultaneous optical and electrical recording of cellular activity and will be used for drug screening and mechanistic studies of gene function implicated in CNS disorders. Novel patterning of neuronal cultures will also enable the study of how localised neurotoxicity spreads to affect neighbouring cells.

Application abstract

Understanding mental health is one of the grand challenges of our age. Brain disorders are top of the World Health Organisation’s agenda due to their impact and prevalence, especially with the ageing population. This has heavy repercussions on the society and has produced a substantial financial burden, estimated to be 3-4% of the gross national product in developed countries. Alongside well-targeted treatments and prevention programmes, technological advances can drive forward our understanding of how neuronal function and communication is affected in central nervous system (CNS) disorders. Miniaturised in vitro methods have long been invaluable as a primary tool for this purpose but conventional techniques do not allow tight control over the parameters that influence the cellular activity and communication as well as their microenvironment. A viable solution to these problems lies in the use of microfluidic procedures which enable greater control over the formation of simplified neuronal networks that mimic in vivo conditions. Available assays in the current conventional biology and miniaturised system arena are characterised by a reduced capability to test neuronal functionality due to the lack of control over the neuronal connectivity and the inability to address neuronal network communication whilst inducing disease conditions.

The aim of this project is to develop novel microfluidic systems for advanced culture and patterning of neurons that will allow simultaneous optical and electrical recording of cellular activity. Development of these systems will be a significant step forward in CNS drug discovery studies, as well as allowing the investigation of cellular and sub-cellular activity under conditions mimicking those proposed to underlie CNS disorders. Positive outcomes from these experiments will provide both platform technologies and methodologies to develop low-cost tools for drug screening and improve our understanding of CNS disorders. We envisage that the successful development of these devices will allow at least a 50% reduction in animal usage, as well as contributing to the replacement of in vivo experiments with sophisticated and functional in vitro models.

Impacts

Publications

  1. MacKerron C et al. (2017). A Microfluidic Platform for the Characterisation of CNS Active Compounds. Scientific Reports 7(1):15692. doi: 10.1038/s41598-017-15950-0