Modeling systems have become a highly promising tool for understanding the mysteries of the brain, one of the biggest scientific challenges of the century. Over the last decade, three dimensional in vitro biological models such as spheroids and brain organoids have emerged, proving to reliably mimic the microenvironment of living tissues and bridge the gap with in vivo animal models. As the spatial distribution of cells in tissue affects gene expression, signal transduction and several biological functions, this 3D approach enables far better disease modelling and preclinical pharmacokinetic studies than its 2D predecessor. Increasing use of this revolutionary technique has, however, revealed the limitations of existing methods for measuring the activity of neurons packed in a 3D environment.

Revolutionizing recording from complex 3D neuronal assemblies

The 'z-dimension' poses serious limits on optical measurements as well as on conventional planar micro electrode arrays (MEAs). Standard cell culture model measuring techniques can only monitor events on the surface of biological samples, thus missing the neuronal processing taking place in the three dimensions.  3Brain , the first company in the world to design and realize high resolution MEAs, has developed a solution that overcomes all these complex technological challenges. "With our new technology we aimed to get inside the tissue and replicate the right environment with continuous cell perfusion so that measurements are much more predictive of what will actually happen in clinical trials," says Mauro Gandolfo, CEO of 3Brain.

3Brain , a CSEM spin-off, developed its new MEA chip in partnership within an  Innosuisse  project. Together, the partners have introduced several innovations. "These include microelectronic circuit design to interface a large neuronal network, post-CMOS MEMs processing to fabricate 3D electrodes and a packaging solution compatible with the culture of biological in vitro models," explains Michel Despont, Vice-President and Head of CSEM's microsystems program, whose team also carried out biological validation with relevant neuronal models. "CSEM's ability to bring together this wide variety of competencies, combined with its long successful relationship with 3Brain, were instrumental in getting the chip for 3D brain tissue modeling to market."