Ima-Go: A High-throughput, Functional Imaging Platform to Accelerate Drug Discovery
The aim of this SME Instruments Phase 1 proposal is to perform a feasibility study for the commercialization of Ima-Go, a novel 96-well functional imaging platform for preclinical drug discovery for substances targeting brain diseases.
In contrast to state-of-the-art technologies for functional imaging, which either interfere with cellular viability and physiology or provide only a poor spatiotemporal resolution, Ima-Go is label-free, non-invasive and provides readouts of highest quality and resolution. The Ima-Go platform will introduce to the market new biological assays for human cell lines, which cannot be performed by current competing technologies.
This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 854430.
MAPSYNE: Miniaturized Automated Patch-Clamp System Combined With High-Density Microelectrode Arrays for Multi-Scale Functional Mapping of Neuronal Networks
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 (https://ec.europa.eu/research/health/). 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. This project aims to develop MAPSYNE, a Miniaturized Automated Patch-clamp SYstem combined with high-density microelectrode arrays (HD-MEAs) for multi-scale functional mapping of NEuronal networks. Patch-clamp allows detection of synaptic events and action potentials (APs) of single cells, while HD-MEAs record APs of thousands of neurons in parallel (also track APs propagating along axons). Combining the two methods will allow access to neuronal electrical signals across spatial and temporal scales.
MAPSYNE’s main objectives are (1) the development of hardware and software for a fully automated mini-patching system on HD-MEAs and (2) proof-of-concept experiments using primary and human induced pluripotent stem cell (h-iPSC)-derived neuronal networks.
MAPSYNE will be designed for long-term, label-free recording of cell cultures. Other applications include local application of drugs (e.g, synaptic blockers on neuronal compartments). After this project, the ER envisions the commercialization of MAPSYNE, and eventually, its usage for preclinical CNS drug discovery.
This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 798836.
STIMOS: Stimulation of Multiple Organoids Simultaneously
This project aims to develop STIMOS, an in-vitro platform to simultaneously stimulate and record from multiple mouse or human derived 3D retinal organoids by high-density multi electrode arrays.
This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 842804.
In-Cytes: In-Cytes A High-Density Microelectrode Array Platform for Large-Scale Intracellular Functional Assays
Our knowledge of the brain and its neurons has increased tremendously over the years. Scientists can now analyse events and structures from the molecular scale up to entire brain regions using a variety of techniques. Electrophysiology measures the flow of ions into and out of cells that is associated with synaptic transmission. Recordings of synchronised activity in large populations of cells are quite common. Recordings of individual membrane potential changes in single cells has also become commonplace. However, recording individual activity in thousands of cells simultaneously at high resolution remains elusive. In-Cytes is developing an electrophysiological platform for such high throughput, high-resolution measurement of interconnected activity to spur drug discovery for debilitating brain diseases.
This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 861712.
NEUREKA: A Smart, Hybrid Neural-Computo Device for Drug Discovery
NEUREKA will bring a paradigm shift in drug discovery for neurological diseases, a sector that suffers multiple, repeated failures exacerbating the economical and societal burden of these incurable diseases. It will do so by addressing a crucial shortcoming: the lack of in vitro systems faithfully reproducing brain pathology that enable the functional assessment of candidate compounds at multiple levels: from synapses to neuronal circuits. NEUREKA introduces an innovative, hybrid technology, whereby detailed, computational neuronal networks simulate dysfunction and drive cultured neurons to replicate in-brain disease conditions. Nanoelectrodes mediate the transmission between simulated and biological neurons. Akin to real synapses, nanoelectrodes contact cultured neurons at subcellular locations across the dendritic tree, soma and axonal branches, allowing to control and monitor neural activity with unprecedented accuracy. Biological neuronal responses registered by nanoelectrodes are fed back to simulated neurons, closing the loop and enabling control of activity states across the hybrid population. Complementing molecular deficits already present in culture models of a disease, computational models enable replication of both molecular and physiological deficits of neurodegeneration in vitro. Cultured neurons are driven towards pathological excitability states where deficits emerge, so as to optimize quantification of the impact of drugs, going well beyond standard cellular assays. A proof-of-concept will be provided for Alzheimer’s disease, using human induced pluripotent stem cell (iPSC)-derived neurons exhibiting the pathology. NEUREKA will be used to demonstrate the effect of drug candidates across synaptic, neuronal and network functions.
This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 863245.