ERC Advanced Grant "neuroXscales"
Microtechnology and integrated microsystems to investigate neuronal networks across scales ("neuroXscales")
The ERC Advanced Grant neuroXscales (external pageGrant Agreement Nº 694829) included employing microtechnology and microelectronics to study neural networks in vitro across scales. Across scales pertains to the spatial domain - from details of subcellular components through single neurons to entire networks - and the temporal domain - from single action potentials to developmental processes. Besides our CMOS-microelectronics-based high-density microelectrode arrays for recording and stimulation, the methodology encompassed patch-clamping, high-resolution confocal microscopy, genetic methods, large-scale data handling strategies, and dedicated data analysis and modeling algorithms. We used mammalian cortical neuron cultures and brain slices.
The high-spatio-temporal-resolution methodology, for example, facilitated investigations of axonal and axonal initial segment signaling characteristics. It also enabled the mapping of the synaptic input to a specific neuron, or the monitoring of action potentials in a network over extended time to see developmental effects or effects of disturbances. Potential applications included research in neural diseases and pharmacology.
The grant started on October 1st, 2016 and ended after 6 years in September 2022.
An ERC proof-of-concept (PoC) project "HD-MEA-based neuronal assays and network analysis for phenotypic drug screenings" (HD-Neu-Screen, external pageGrant Agreement N° 875609) has been executed between January 1st, 2020 and June 30th, 2021. The goal of this ERC-PoC-project was to translate and commercialize - in collaboration with the spin-off company external pageMaxWell Biosystems - the assessment of characteristic electrophysiological features of subcellular neuronal components, individual neurons and neuronal networks, all of which can be obtained with high-density microelectrode array technology, into functional neuronal assays for drug screening.
Relevant Publications
T. Kim, D. Chen, P. Hornauer, V. Emmenegger, J. Bartram, S. Ronchi, A. Hierlemann, M. Schröter, D. Roqueiro, "Predicting in vitro single-neuron firing rates upon pharmacological perturbation using graph neural networks", Frontiers in Neuroinformatics 2022, Vol. 16, Article 1032538 (DOI: 10.3389/fninf.2022.1032538). external pageOnline
X. Xue, A. P. Buccino, S. Saseendran Kumar, A. Hierlemann, and J. Bartram, "Inferring monosynaptic connections from paired dendritic spine Ca2+ imaging and large-scale recording of extracellular spiking", Journal of Neural Engineering 2022, 19 (4), Article 046044 (DOI: 10.1088/1741-2552/ac8765). external pageOnline
M. Schröter, C. Wang, M. Terrigno, P. Hornauer, Z. Huang, R. Jagasia, A. Hierlemann, "Functional imaging of brain organoids using high-density microelectrode arrays", MRS Bulletin 2022, Vol. 47, p 530–544 (DOI: 10.1557/s43577-022-00282-w). external pageOnline
S. Kumar, T. Gänswein, A. Buccino, X. Xue, J. Bartram, V. Emmenegger, A. Hierlemann, "Tracking axon initial segment plasticity using high-density microelectrode arrays: A computational study", Frontiers in Neuroinformatics 2022, Vol. 16, Article 957255 (DOI: 10.3389/fninf.2022.957255). external pageOnline
A. Buccino, X. Yuan, V. Emmenegger, X. Xue, T. Gänswein, A. Hierlemann, "An automated method for precise axon reconstruction from recordings of high-density micro-electrode arrays", Journal of Neural Engineering 2022, 19 (2), Article 026026 (DOI: /10.1088/1741-2552/ac59a2). external pageOnline
X. Yuan, A. Hierlemann, U. Frey, "Extracellular recording of entire neural networks using a dual-mode microelectrode array with 19,584 electrodes and high SNR", IEEE Journal of Solid-State Circuits 2021, Vol. 56(8), pp. 2466-2475 (DOI: 10.1109/JSSC.2021.3066043). external pageOnline
S. Ronchi, A. Buccino, G. Prack, S. Kumar, M. Schröter, M. Fiscella, A. Hierlemann, "Electrophysiological phenotype characterization of human iPSC‐derived neuronal cell lines by means of high‐density microelectrode arrays", Advanced Biology 2021, Article 2000223 (DOI: 10.1002/adbi.202000223). external pageOnline
X. Yuan, M. Schröter, M. Engelene J. Obien, M. Fiscella, W. Gong, T. Kikuchi, A. Odawara, S. Noji, I. Suzuki, J. Takahashi, A. Hierlemann, U. Frey, "Versatile live-cell activity analysis platform for characterization of neuronal dynamics at single-cell and network level", Nature Communications 2020, 11, 4854 (DOI: 10.1038/s41467-020-18620-4). external pageOnline
M. Kollo, R. Racz, M.-E. Hanna, A. Obaid, M.R. Angle, W. Wray, Y. Kong, J. Müller, A. Hierlemann, N. A. Melosh, A.T. Schaefer, "CHIME: CMOS-hosted in vivo microelectrodes for massively scalable neuronal recordings", Front. Neurosci. 2020, 14:834 (DOI: 10.3389/fnins.2020.00834). external pageOnline
A. Obaid, M. E. Hanna, Y.-W. Wu, M. Kollo, R. Racz, M. R. Angle, J. Müller, N. Brackbill, W. Wray, F. Franke, E. J. Chichilnisky, A. Hierlemann, J. B. Ding, A. T. Schaefer, N. A. Melosh, "Massively parallel microwire arrays integrated with CMOS chips for neural recording", Science Advances 2020, 6 (12), Article eaay2789 (DOI: 10.1126/sciadv.aay2789). external pageOnline
V. Viswam, M. Engelene Obien, F. Franke, U. Frey, A. Hierlemann, "Optimal electrode size for multi-scale extracellular-potential recording from neuronal assemblies", Frontiers in Neuroscience 2019, 13, Article 385 (DOI: 10.3389/fnins.2019.00385). external pageOnline
V. Emmenegger, M. Engelene Obien, F. Franke, A. Hierlemann, "Technologies to study action potential propagation with a focus on HD-MEAs", Frontiers in Cellular Neuroscience 2019, 13, Article 159 (DOI: 10.3389/fncel.2019.00159). external pageOnline
S. Ronchi, M. Fiscella, C. Marchetti, V. Viswam, J. Müller, U. Frey, A. Hierlemann, "Single-cell electrical stimulation using CMOS-based high-density microelectrode arrays", Frontiers in Neuroscience 2019, 13, Article 208 (DOI: 10.3389/fnins.2019.00208). external pageOnline
M. Engelene Obien, A. Hierlemann, U. Frey, "Accurate signal-source localization in brain slices by means of high-density microelectrode arrays", Scientific Reports 2019, Vol. 9, Article 788 (DOI: 10.1038/s41598-018-36895-y). external pageOnline
T. Bullmann, M. Radivojevic, S. Huber, K. Deligkaris, A. Hierlemann, U. Frey, "Large-scale mapping of axonal arbors using high-density microelectrode arrays", Frontiers in Cellular Neuroscience 2019, 13, Article 404 (DOI: 10.3389/fncel.2019.00404) external pageOnline.
D. Bakkum, M. Engelene J. Obien, M. Radivojevic, D. Jäckel, U. Frey, H. Takahashi, A. Hierlemann, "The axon initial segment is the dominant contributor to the neuron's extracellular electrical potential landscape", Advanced Biosystems 2018, 1800308 (DOI: 10.1002/adbi.201800308). external pageOnline
A. Shadmani, V. Viswam, Y. Chen, R. Bounik, J. Dragas, M. Radivojevic, S. Geissler, S. Sitnikov, J. Müller, A. Hierlemann, "Stimulation and artifact-suppression techniques for in-vitro high-density microelectrode array systems", IEEE Transactions on Biomedical Engineering, 2018, in press (DOI: 10.1109/TBME.2018.2890530). external pageOnline
R. Diggelmann, M. Fiscella, A. Hierlemann, F. Franke, "Automatic Spike Sorting Algorithm for High-Density Microelectrode Arrays", Journal of Neurophysiology 2018, 120 (6), pp. 3155–3171 (DOI: 10.1152/jn.00803.2017). external pageOnline