High-resolution CMOS MEA platform to study neurons at subcellular, cellular, and network levels

Abstract

Studies on information processing and learning properties of neuronal networks would benefit from simultaneous and parallel access to the activity of a large fraction of all neurons in such networks. Here, we present a CMOS-based device, capable of simultaneously recording the electrical activity of over a thousand cells in in vitro neuronal networks. The device provides sufficiently high spatiotemporal resolution to enable, at the same time, access to neuronal preparations on subcellular, cellular, and network level. The key feature is a rapidly reconfigurable array of 26 400 microelectrodes arranged at low pitch (17.5 μm) within a large overall sensing area (3.85 × 2.10 mm(2)). An arbitrary subset of the electrodes can be simultaneously connected to 1024 low-noise readout channels as well as 32 stimulation units. Each electrode or electrode subset can be used to electrically stimulate or record the signals of virtually any neuron on the array. We demonstrate the applicability and potential of this device for various different experimental paradigms: large-scale recordings from whole networks of neurons as well as investigations of axonal properties of individual neurons.

Direct interfacing of neurons to highly integrated microsystems

“…It was also possible to detect small signals of action potentials traveling along thin axons (~100 nm diameter) as shown in Figure 5 center and right panels [27,28]. Axonal signals across a branching point were recorded by simultaneously using 841 electrodes.…”

“…In this contribution, we will demonstrate how highly integrated CMOS microelectrode array systems featuring several thousands of transducers (> 3'000 transducers per mm 2 ) can be used to record from or stimulate potentially any individual neuron or subcellular compartment on a CMOS chip [4,21,26,28].…”

“…3 a HD-MEA system featuring a sensing area of 3.85 × 2.10 mm 2 hosting 26'400 Pt electrodes of 7 µm diameter at a center-to-center pitch of 17. µm [26,28]. The switch matrix allows for simultaneously routing user-configurable selections of electrodes to 1024 recording channels with 10-bit 20-kS/s A/D conversion and 32 stimulation units at the array periphery.…”

“…CMOS (complementary metal oxide semiconductor) technology-based planar, high-density microelectrode arrays (HD-MEAs) feature several thousands of transducers at densities of > 3'000 transducers per mm 2 [4,18,[21][22][23][24][25][26] (Figure 1), which enables recordings from large neuronal networks at single-cell, or even subcellular-component resolution [27,28]. The integrated systems feature tightly-spaced transducers and the respective addressing and readout circuitry on a single chip [4,[21][22][23][24][25][26].…”

Fabrication and electrochemical characterization of ruthenium nanoelectrodes

“…The integration of MEAs in a complementary metal oxide semiconductor integrated circuit (CMOS IC) enables complex, programmable measurements and stimulation of cells on a small chip [2]. Extracellular electrodes allow the recording and stimulation of cells on a subcellular, cellular and on a network level [3][4] [5]. If the electrodes are sufficiently small -i.e.…”