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.

To advance our understanding of the functioning of neuronal ensembles, systems are needed to enable simultaneous recording from a large number of individual neurons at high spatiotemporal resolution and good signal-to-noise ratio. Moreover, stimulation capability is highly desirable for investigating, for example, plasticity and learning processes. Here, we present a microelectrode array (MEA) system on a single CMOS die for in vitro recording and stimulation. The system incorporates 26,400 platinum electrodes, fabricated by in-house post-processing, over a large sensing area (3.85 × 2.10 mm 2 ) with sub-cellular spatial resolution (pitch of 17.5 μm). Owing to an area and power efficient implementation, we were able to integrate 1024 readout channels on chip to record extracellular signals from a user-specified selection of electrodes. These channels feature noise values of 2.4 μV rms in the action-potential band (300 Hz-10 kHz) and 5.4 μV rms in the local-field-potential band (1 Hz-300 Hz), and provide programmable gain (up to 78 dB) to accommodate various biological preparations. Amplified and filtered signals are digitized by 10 bit parallel single-slope ADCs at 20 kSamples/s. The system also includes 32 stimulation units, which can elicit neural spikes through either current or voltage pulses. The chip consumes only 75 mW in total, which obviates the need of active cooling even for sensitive cell cultures. I IntroductionEXTRACELLULAR RECORDINGS of the electrical activity of neural and cardiac cell networks in organs such as the brain, the retina, or the heart, can provide a wealth of information about the physiology as well as the pathological degenerations that may cause diseases, such as Parkinson's or Alzheimer's. Microelectrode arrays (MEAs) have been used for a long time for in vitro extracellular recordings of electrogenic cell cultures and tissues, such as acute or organotypic brain slices and retinae [1]- [3]. They provide simultaneous multisite recording capability, which is essential to study cellular interconnections and network properties that arise from synchronized cellular activity [4], [5]. However, passive MEAs, which typically include metal electrodes on a glass substrate, are limited in both the number of electrodes (usually less than 300) and the spatial resolution (typically ≥ 30 μm),features that are needed to reconstruct large neural networks at cellular detail.With CMOS technology, these limitations can be overcome by using multiplexing techniques, which enable access to a large number of closely-spaced electrodes to obtain large sensing areas at high spatial resolution [6]. Moreover, the monolithic integration of recording amplifiers and ADCs, on the same substrate with the electrodes, avoids off-chip parasitics and interference and, at the same time, allows for realizing a large number of recording channels with a low number of connections. In this paper, we present a recently developed CMOS MEA system that further exploits the switch-matrix approach. The system preserves s...

Planar microelectrode arrays (MEAs) are devices that can be used in biomedical and basic in vitro research to provide extracellular electrophysiological information about biological systems at high spatial and temporal resolution. Complementary metal oxide semiconductor (CMOS) is a technology with which MEAs can be produced on a microscale featuring high spatial resolution and excellent signal-to-noise characteristics. CMOS MEAs are specialized for the analysis of complete electrogenic cellular networks at the cellular or subcellular level in dissociated cultures, organotypic cultures, and acute tissue slices; they can also function as biosensors to detect biochemical events. Models of disease or the response of cellular networks to pharmacological compounds can be studied in vitro, allowing one to investigate pathologies, such as cardiac arrhythmias, memory impairment due to Alzheimer's disease, or vision impairment caused by ganglion cell degeneration in the retina.

A current-mode conductance-based silicon neuron for address-event neuromorphic systems Livi, P; Indiveri, G Livi, P; Indiveri, G (2009 A current-mode conductance-based silicon neuron for address-event neuromorphic systems AbstractSilicon neuron circuits emulate the electrophysiological behavior of real neurons. Many circuits can be integrated on a single very large scale integration (VLSI) device, and form large networks of spiking neurons. Connectivity among neurons can be achieved by using time multiplexing and fast asynchronous digital circuits. As the basic characteristics of the silicon neurons are determined at design time, and cannot be changed after the chip is fabricated, it is crucial to implement a circuit which represents an accurate model of real neurons, but at the same time is compact, low-power and compatible with asynchronous logic. Here we present a current-mode conductance-based neuron circuit, with spike-frequency adaptation, refractory period, and bio-physically realistic dynamics which is compact, low-power and compatible with fast asynchronous digital circuits.A current-mode conductance-based silicon neuron for Address-Event neuromorphic systems bstract-Silicon neuron circuits emulate the electrophysiological behavior of real neurons. Many circuits can be integrated on a single Very Large Scale Integration VLSI) device, and form large networks of spiking neurons. Connectivity among neurons can be achieved by using time multiplexing and fast asynchronous digital circuits. As the basic characteristics of the silicon neurons are determined at design time, and cannot be changed after the chip is fabricated, it is crucial to implement a circuit which represents an accurate model of real neurons, but at the same time is compact, low-power and compatible with asynchronous logic. Here we present a current-mode conductancebased neuron circuit, with spike-frequency adaptation, refractory period, and bio-physically realistic dynamics which is compact, low-power and compatible with fast asynchronous digital circuits.

We present a monolithic complementary metal-oxide semiconductor (CMOS)-based sensor system comprising an array of silicon nanowire field-effect transistors (FETs) and the signal-conditioning circuitry on the same chip. The silicon nanowires were fabricated by chemical vapor deposition methods and then transferred to the CMOS chip, where Ti/Pd/Ti contacts had been patterned via e-beam lithography. The on-chip circuitry measures the current flowing through each nanowire FET upon applying a constant source-drain voltage. The analog signal is digitized on chip and then transmitted to a receiving unit. The system has been successfully fabricated and tested by acquiring I-V curves of the bare nanowire-based FETs. Furthermore, the sensing capabilities of the complete system have been demonstrated by recording current changes upon nanowire exposure to solutions of different pHs, as well as by detecting different concentrations of Troponin T biomarkers (cTnT) through antibody-functionalized nanowire FETs.

We report on a compact (0.02 mm(2) ) buffer for both voltage and current stimulation of electrogenic cells on a complementary metal-oxide semiconductor microelectrode array. In voltage mode, the circuit is a high-current class-AB voltage follower, based on a local common-mode feedback (LCMFB) amplifier. In current mode, the circuit is a current conveyor of type II, using the same LCMFB amplifier with cascode stages to increase the gain. The circuit shows good linearity in the 0.5-3.5 V input range and has extensively been used for stimulation of neuronal cultures.

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