Cell-based assays analyse cells placed in plastic dishes. Standard approaches provide for extracting information from cells through optical systems or sensors embedded in the plastic substrate (e.g. passive microelectrode array – MEA – technology). The information acquired from the cells travel on limited bandwidth across long distances (compared to the cell’s size) before reaching a CPU on a paired machine where this information will be processed.
Long distances affect the quality of the information and bandwidth issues limit the quantity of information that can be transmitted to a few frames per second through imaging or a few sensors in a MEA. However, cells’ behaviour arises from complex collective interactions between large populations of cells.
Then a change in paradigm is requiredto gain insights into cell network processing and the mechanisms of life.
At 3Brain we have devised the CorePlate™ technology to transform the standard plastic dishes used by researchers for many years to study cell networks into an intelligent device. Each well now integrates a semiconductor processing core, namely a BioSPU (BioSignalProcessing Unit), that pairs with the cell processing network. The BioSPU core pre-processes cell data in-situ, efficiently, with neither speed nor band limits and with the best quality output.
Brain research utilizes different techniques to study cells networks such as high content screening (HCS), patch-clamp and microelectrode array (MEA). All these techniques provide meaningful insights into the biological processes of neuronal cells, but they all fail to bring a comprehensive and accurate pictureof the cell network dynamics.
When it comes to kinetic assays on live cells, HCS is hindered by many obstacles such asphototoxicity, photobleaching, temporal resolution, dye-mediated modification of cell physiology, etc. Patch-clamp brings high details in single-cell and single-channel analysis but cannot capture network-wide processes. Similarly, cell network investigations with MEA passive technology are impaired by significant undersampling (few electrodes per thousands of cells), resulting in poor statistics and questionable results.
The CorePlate™ technology brings a processing core in contact with the cell network. The silicon BioSPU core in CMOS technology allows to integrate thousands of sensors and actuators in few square millimetres and its processing speed represent a perfect match to the processing power of the cell network.
Since the early 2000s, we at 3Brain have worked to push the boundaries of CMOS technology applied to cell networks and become a leader in the field of high-resolution electrophysiological platforms.
As the first company to optimize CMOS technology for electrogenic cells, we have overcome the challenges that have come along with this novel technology. Our engineers have worked diligently to continue releasing new and improved circuit designs that best fit the needs of researchers working with neuronal and cardiac cells. From generation 0 to the generation 3 (Khíron chip) and the next line currently under development, it is our knowledge and years of experience that culminate into better and better CMOS-MEAs.
The in-vitro field is constantly evolving. The rise of human-derived stem cell technology and the progression toward more in vivo-like human models raise new challenges in identifying reliable and efficient readout technology. For this reason, we at 3Brain are committed to the constant development of innovative products - like the 3D CMOS chip - to maximize the potential of the dense information acquired from advanced in-vitro models such as human-derived organoids or spheroids.