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Miniaturized automated patch-clamp system combined with high-density microelectrode arrays for multi-scale functional mapping of neuronal networks

Periodic Reporting for period 1 - MAPSYNE (Miniaturized automated patch-clamp system combined with high-density microelectrode arrays for multi-scale functional mapping of neuronal networks)

Reporting period: 2018-12-01 to 2020-11-30

More than one billion people worldwide (165 million in Europe) suffer from diseases of the central nervous system (CNS). With Europe's aging societies, the European Commission identified brain research as one of the key research areas under healthcare.

Many neurodegenerative diseases are still without cure (e.g. Parkinson’s, amyotrophic lateral sclerosis (ALS) and Alzheimer’s) and repeated failures in clinical trials increase the demand for novel screening technologies to be implemented in the early phases of drug discovery.

Recent studies show that synaptic dysfunction is involved in CNS diseases.

New technologies for neuronal screening targeting synaptic and network activity, combined with disease model cells in vitro, will enable novel functional assays for CNS drug discovery.

MAPSYNE project objective is to develop a miniaturized automated patch-clamp system combined with high-density microelectrode arrays (HD-MEAs) for multi-scale functional mapping of neuronal networks.
The main result achieved is the development of MAPSYNE, a miniaturized and automated system combining a high-density microelectrode array (HD-MEA) and a movable micropipette for studying, monitoring, and perturbing neurons in vitro.

The system involves an all-electrical approach to automatically move a glass micropipette towards a target location on the HD-MEA surface, without the need for a microscope.

Two methods of performing blind navigation are employed, (i) stop-measure-go approach where in the pipette moves for a predefined distance before measuring its location then the process is repeated until the pipette reaches its destination, and (ii) predictive approach wherein the pipette is continuously tracked and moved. This automated system can be applied for unsupervised single-cell manipulation of neurons in a network, such as electroporation and local delivery of compounds
Thanks to automation, multiple neurons in a cell culture can be reached by a pipette in a short amount of time. This system can be applied for unsupervised local delivery of compounds to single-cells. With the current speed of the system, it is possible to automatically target 100 cells for local-puffing of compounds in less than 50 minutes.
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