9:16 AM - *SM03.01.07
CMOS Microelectronic Systems to Characterize Neurons and Networks at Subcellular Resolution
Microelectrode arrays (MEAs) have been widely used in recent years for in-vitro investigation of neuronal cells and neural networks, as they enable long-term bi-directional interfacing with networks of living cells [1, 2]. Modern CMOS-based active MEA devices, especially high-density MEAs, provide the capability to simultaneously perform electrophysiological recordings from thousands of electrodes at cellular/subcellular spatial resolution [3-6]. The high spatio-temporal resolution enables better separation and assignment of neural activities for closely spaced neurons as well as localized and specific stimulation of single individual neurons .
An exemplary CMOS high-density microelectrode system includes a large sensing area of 4.48 × 2.43 mm2 comprising 59’760 (332 × 180) electrodes of 3 × 7.5 µm2 size at a pitch of 13.5 µm . The system incorporates several types of sensing units with the aim of extracting a wide spectrum of information from the same neuronal culture or brain slice: 16 dual-mode stimulation buffers, 2048 action-potential recording channels, 32 local-field-potential recording channels, 32 current recording units, 32 impedance measurement units and 28 neurotransmitter detection units .
By using such a system it was possible to record subcellular-resolution data in various preparations, ranging from organotypic and acute slices to cultures of dissociated neurons and stem-cell derived neurons. It was also possible to detect low-amplitude signals of action potentials traveling along thin axons (~100 nm diameter). Moreover, the stimulation features of CMOS microtransducer arrays and integrated microsystems offer the capability to bi-directionally interact, also in closed loop and real time, with potentially every single neuron in a given neuronal network. Applications include research in neural diseases and pharmacology.
The work was supported by the European Community through the ERC Advanced Grant “neuroXscales” under contract number AdG 694829.
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