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Contenu archivé le 2022-12-23

High-Resolution Lateral Imaging of Neurological Activity Using Novel Sensitive Micro-Biosensors

Objectif

Analysis systems allowing highly sensitive, selective and rapid determination of key analytes such as neurotransmitters are of vital interest for medical research, especially for the elucidation of brain function. The elucidation of the chemical background of cell-to-cell communication would contribute to understand the fundaments of some neurodegenerative diseases (e.g. Alzheimer, Parkinson), the memory and learning process, or to evaluate the neurotoxic effects of different drugs. Adequate information in real time about the altered concentration of key neurotransmitters (e.g. glutamate) would possibly lead to new efficient therapies. To address these aspects is motivated not only from a scientific, but also from an economic and social point of view, since the increase of aged population resulted in an increased percentage of patients suffering from the above mentioned diseases, causing exorbitant costs to the healthcare systems and painful emotional stresses to patients, relatives and personnel involved in medical care.
An ideal analysis system should allow sampling from a defined brain area and should yield a continuous, selective and highly sensitive signal within milliseconds. Neither the existing classical analytical methods nor the reported biosensors fulfil entirely these requirements. Glutamate is known to play a vital role in these processes but its functional mechanism is not fully elucidated since the existing analytical methods do not permit its real-time and localised monitoring. Therefore the present project targets the development of a novel microanalysis system for timely, selective and highly sensitive monitoring of glutamate and its validation in two different neurobiological research areas. The envisaged microanalysis system is composed by a specially designed micro-chambered dual electrode cell integrated with highly sensitive and selective micro-biosensors based an redox polymer-entrapped glutamate oxidase.

The project will focus on the development and characterisation of each structural element of the analysis system expressed in five main tasks namely:

- construction of the novel micro-chambered, dual electrode cell which will allow a redundant and localised monitoring both from model solutions and brain slices;
- bioengineering and characterisation of a novel glutamate oxidase with improved selectivity and stability;
- engineering of an efficient electron-transfer pathway between enzyme and electrode surface via novel highly permeable redox polymers based on osmium and/or ruthenium complexes to be synthesised and evaluated;
- sensor development using the novel enzyme and redox polymers
- miniaturisation of enzyme electrodes and their integration into a scanning electrochemical microscope for visualization.

Additionally the developed novel micro-analysis system will be tested and evaluated in two model neurobiological experiments, focusing on the elucidation of
(i) the memory and learning process (imprinting) and;
(ii) neurotoxic effects of amphetamin-like drugs.
The outcome of the project is important both for fundamental (e.g. isolation and production of novel enzyme, engineering of electron-transfer pathways, synthesis of novel redox polymers) and applied research (development of a redundant analysis system with integrated biosensors for medical application).

The expected results will go far beyond the hereby presented exemplary applications in neurobiological experiments, since
(i) will bring novel enzymes and mediator on the market;
(ii) will spin-off the development of other analytical fields not only in clinical analysis, but also environmental control and;
(iii) will promote micro-scaled research via the development of novel microtools (e.g. immobilization methods, visualization).

Appel à propositions

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Régime de financement

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Coordinateur

Ruhr Universitat Bochum
Contribution de l’UE
Aucune donnée
Adresse
Universitatsstr. 150
44780 Bochum
Allemagne

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Coût total
Aucune donnée

Participants (5)