The programmable brain-on-a-chip
Dries Braeken, Stein Aerts, Catherine Verfaillie, Peter Peumans
Bart De Strooper, Ludo Van Den Bosch, Patrik Verstreken, Pierre Vanderhaeghen
Philip Van Damme, Wim Vandenberghe
Past failures in therapeutic development have shown that context is everything when studying complex human brain diseases. There are no animal models that fully mimic all different aspects of the disease process or all symptoms that accompany for example Alzheimer’s or Parkinson’s disease. This lack of reliable models to study disease, is a severe limitation for scientists and the pharmaceutical industry.
It is our mission to ‘humanize’ dementia research, and we mean this literally. We will create 2D screening platforms, 3D networks but also live models, all using human brain cells that recapitulate what goes on (or wrong) in the brain. We will not merely grow human cells on plastic, but forge complex interactions, or even chimeric models, so that we can continuously monitor what happens within cells and networks.
By bringing together novel technology, clinical expertise and rigorous cell biology, we will build new tools, enabling the discovery of new targets and the development of better platforms for high-throughput drug candidate screening.
Imec’s advanced chip technologies will allow for high throughput interrogation of engineered three-dimensional neuronal circuits on a single-cell level. Bringing our platform technologies together with human stem cell lines from patients will aid in the development of better models for neurodegenerative diseases.
Mora Lopez et al. ISSCC 2018 on Feb 14, 2018 in session 29: Advanced Biomedical Systems at 2.30 pm: 29.3 – A 16384-Electrode 1024-Channel Multimodal CMOS MEA for High-Throughput Intracellular Action Potential Measurements and Impedance Spectroscopy in Drug-Screening Applications.
Researchers at imec have designed and fabricated a 16,384-electrode, 1,024-channel micro-electrode array (MEA) for high-throughput multi-modal cell interfacing. The chip offers intracellular and extracellular recording, voltage- and current-controlled stimulation, impedance monitoring and spectroscopy functionalities thereby packing the most cell-interfacing modalities on a single chip, and being the only one to enable multi-well assays. With this new chip, imec has created a platform that enables high quality data acquisition at increased throughput in cell-based cell studies.
Espuny Camacho et al. Neuron 2017. Hallmarks of Alzheimer's Disease in Stem-Cell-Derived Human Neurons Transplanted into Mouse Brain.
Researchers from the lab of professor Bart De Strooper (VIB/KU Leuven) successfully transplanted human neural cells into mouse brains containing amyloid plaques, one of the hallmarks of Alzheimer’s disease. Unlike mouse neurons, human neurons that developed in this environment were extremely susceptible to Alzheimer’s disease.
Guo et al. Nature Communications 2017. HDAC6 inhibition reverses axonal transport defects in motor neurons derived from FUS-ALS patients.
The teams led by professor Ludo Van Den Bosch (VIB/KU Leuven) and Catherine Verfaillie (KU Leuven) used stem cell technology to generate motor neurons from ALS patients carrying mutations in FUS. They found disturbed axonal transport in these motor neurons, but also identified genetic and pharmacological strategies that mitigate these defects in cells.
Ju et al. Nature 2017. Fully integrated silicon probes for high-density recording of neural activity.
Engineers and scientists at imec, KU Leuven and VIB collaborated with researchers at HHMI’s Janelia Research Campus, the Allen Institute, and University College London (with grant funding from Gatsby and Wellcome) to build and test powerful new devices for detecting neural activity within the brains of living animals. The result is a silicon probe called Neuropixels, which can simultaneously record the activity of more than 200 individual neurons.
Imec does not only develop multi-electrode probes to probe brain activity, but also probes that can stimulate the activity of brain cells by shining light on them. Such probes can be used for ‘optogenetics’, a technique combining genetics and optics.