Summary Mammalian brains consist of 10s of millions to 100s of billions of neurons operating at millisecond time scales, of which current recording techniques only capture a tiny fraction. Recording techniques capable of sampling neural activity at such temporal resolution have been difficult to scale: The most intensively studied mammalian neuronal networks, such as the neocortex, show layered architecture, where the optimal recording technology samples densely over large areas. However, the need for application-specific designs as well as the mismatch between the threedimensional architecture of the brain and largely two-dimensional microfabrication techniques profoundly limits both neurophysiological research and neural prosthetics. Here, we propose a novel strategy for scalable neuronal recording by combining bundles of glass-ensheathed microwires with large-scale amplifier arrays derived from commercial CMOS of in-vitro MEA systems or high-speed infrared cameras. High signal-to-noise ratio (&lt;20 μV RMS noise floor, SNR up to 25) is achieved due to the high conductivity of core metals in glass-ensheathed microwires allowing for ultrathin metal cores (down to &lt;1 μm) and negligible stray capacitance. Multi-step electrochemical modification of the tip enables ultra-low access impedance with minimal geometric area and largely independent of core diameter. We show that microwire size can be reduced to virtually eliminate damage to the blood-brain-barrier upon insertion and demonstrate that microwire arrays can stably record single unit activity. Combining microwire bundles and CMOS arrays allows for a highly scalable neuronal recording approach, linking the progress of electrical neuronal recording to the rapid scaling of silicon microfabrication. The modular design of the system allows for custom arrangement of recording sites. Our approach of employing bundles of minimally invasive, highly insulated and functionalized microwires to lift a 2-dimensional CMOS architecture into the 3rd dimension can be translated to other CMOS arrays such as electrical stimulation devices.

CHIME: CMOS-hosted in-vivo microelectrodes for massively scalable neuronal recordings