A new gold standard for electrical measurement in the emerging in vitro world of three dimensional models. That's what Swiss medtech 3Brain has established by partnering with CSEM. Its Khíron chip enables fast, accurate intra-tissue measurement and continuous nutrient and oxygen supply through all tissue layers for the first time. And it is set to unlock the potential of next-generation cell culture models in disease modeling and preclinical studies.
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."
Improving disease understanding and drug development success
Named Khíron, the new application-specific integrated circuit (ASIC) provides a high density MEA specifically targeting intra-tissue measurement of a 3D structure in vitro models by integrating a micro-needle for each electrode for in vitro penetration of brain tissue. It also includes a microfluidic structure at the base of the chip for fluidic exchange even from the bottom layers, unlike most conventional MEA devices.
"The Khíron chip gives neuroscientists the tool they have been waiting for to solve their problems and acquire the information they want from 3D in vitro models" says Dr Gandolfo. "I think it will have a big impact in disease modeling for Alzheimer's and Parkinson's and also in the study of conditions like epilepsy and autism."
3Brain will present Khíron at the SfN Society for Neuroscience annual meeting 2018 (3-7 Nov). The company will introduce its innovation to the market in 2019, initially targeting laboratories and universities interested in undertaking validation studies. It will then be integrated into the next generation of its products for the pharmaceutical and biotechnology sectors. 3Brain expects its new technology to double sales in two years.