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Biomimicking model of a neuronal pathway

In this project we develop a Brain-on-a-Chip in vitro system for the study of propagative neuronal disorders. The predefined signal sequences within a co-culture network mimic specific brain pathways in the human brain which are predominantly affected by neurodegenerative processes during Dementia, Parkinson or Alzheimer. The combination of this microfluidic platform with a Multi-Electrode Array (MEA) will allow us to investigate morphological and electrophysiological characteristics of neuronal networks on the single cell function.


Schematic of funnel shaped microchannels, the“AxonDiode” microfluidic, to separate two cellular networks . Predefined microchannels with a length of 576µm induce axonal projection and connectivity between the co-culture system with high polarity (>90%).


Picture of our Brain-on-a-Chip sample illustrates the Multi-Electrode Array (MEA) with embebbed microfluidic layer. The positioning of the 64 electrodes is demonstrated in the inlet, showing the alignment to the microfluidic which provides recording of Action Potentials from the first network to the other through the interconnecting axons. This sample could become a great in-vitro tool for investigating neurodegenerative diseases.


Biomimicking_model_of_a_neuronal_pathway_3

Fluorescence imaging analysis of two individual neuronal types in this µfluidic system to characterize the cultured cellular systems. This Image shows a matured co-culture network (Left: Cortical neurons, Right: Striatal neurons, DIV21) in an AxonDiode Microfluidic stained against MAP2 (green) and Synaptophysine (blue) to identify neurons and synaptic connections/junctions. With the use of this µfluidic system it is possible to precisely analyze the synaptical dysfunction during the Alzheimer’s disease and focuses hereby on the brain pathway between cortex and striatum. [Scalebar: 20µm]


Biomimicking_model_of_a_neuronal_pathway_4

The network activity can be investigated by electrical and optical methods. Voltammetric recordings of two neighbour electrodes show Action Potential propagation in the microchannels from the cortical to the striatal neuronal network (Left). Calcium Imaging analysis varifies the information flow in the polarized direction by tracking a fluorescence signal associated with calcium waves (Right).

Additional Information

Contact:

Prof. Dr. Andreas Offenhäusser

Tel.:  +49-2461-61-2330
e-mail: a.offenhaeusser@fz-juelich.de

More Information

Funding:

This work is funded by the ERA-NET NEURON “MICRODEG” project

Publications:

Nanostructured cavity devices for extracellular stimulation of HL-1 cells
Czeschik et al., Nanoscale, 2015, 7, 9275

Engineering connectivity by multiscale micropatterning of individual populations of neurons
Albers et al., Biotechnol. J., 2015, 10

Collaboration Partners:

Jean-Michel Peyrin (Degenerative processes in neurons and networks)
Jean-Louis Viovy (Macromolecules and Microsystems in Biology and Medicine)
Anselme Perrier (I-Stem, Neurodegenerative diseases)
Joaquín Castilla (Proteomics, Prion lab)



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