Marco Ballini

Switch-Matrix-Based High-Density Microelectrode Array in CMOS Technology

We report on a CMOS-based microelectrode array (MEA) featuring 11, 011 metal electrodes and 126 channels, each of which comprises recording and stimulation electronics, for extracellular bidirectional communication with electrogenic cells, such as neurons or cardiomyocytes. The important features include: (i) high spatial resolution at (sub)cellular level with 3150 electrodes per mm2 (electrode diameter 7 ¿m, electrode pitch 18 ¿m); (ii) a reconflgurable routing of the recording sites to the 126 channels; and (iii) low noise levels.

A 1024-Channel CMOS Microelectrode Array With 26,400 Electrodes for Recording and Stimulation of Electrogenic Cells In Vitro

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 ) 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 in the action-potential band (300 Hz-10 kHz) and 5.4 μV 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.

Depth recording capabilities of planar high-density microelectrode arrays

We use a planar, CMOS-based microelectrode array (MEA) featuring 3,150 metal electrodes per mm2 and 126 recording channels to record spatially highly resolved extracellular action potentials (EAPs) from Purkinje cells (PCs) in acute cerebellar slices. An Independent-Component-Analysis-based (ICA) spike sorter is used to reveal EAPs of single cells at subcellular resolution. Those EAPs are then used to set up a compartment model of a PC. The model is used to make and finetune estimations of the distance between MEA surface and PC soma. This distance is estimated using the amplitude-independent part of the shape of the EAPs obtained from recordings. The estimation shows that, in our preparations, we can record from PCs with the center of their soma at approximately 35 µm and 90 µm vertical distance to the chip surface.

Time Multiplexed Active Neural Probe with 1356 Parallel Recording Sites

We present a high electrode density and high channel count CMOS (complementary metal-oxide-semiconductor) active neural probe containing 1344 neuron sized recording pixels (20 µm × 20 µm) and 12 reference pixels (20 µm × 80 µm), densely packed on a 50 µm thick, 100 µm wide, and 8 mm long shank. The active electrodes or pixels consist of dedicated in-situ circuits for signal source amplification, which are directly located under each electrode. The probe supports the simultaneous recording of all 1356 electrodes with sufficient signal to noise ratio for typical neuroscience applications. For enhanced performance, further noise reduction can be achieved while using half of the electrodes (678). Both of these numbers considerably surpass the state-of-the art active neural probes in both electrode count and number of recording channels. The measured input referred noise in the action potential band is 12.4 µVrms, while using 678 electrodes, with just 3 µW power dissipation per pixel and 45 µW per read-out channel (including data transmission).

22.7 A 966-electrode neural probe with 384 configurable channels in 0.13µm SOI CMOS

In vivo recording of neural action-potential (AP) and local-field-potential (LFP) signals requires the use of high-resolution penetrating probes. Driven by the need for large-scale recording and minimal tissue damage, a technology roadmap has been defined for next-generation probes aiming to maximize the number of recording sites while minimizing the probe dimensions [1]. In this paper we present a 384-channel configurable active neural probe for high-density recording which implements in situ buffering under each electrode to minimize the crosstalk between adjacent metal lines along the shank and other parasitic effects inherent to traditional passive probes [2]. Up to 966 selectable, neuron-sized electrodes (12×12μm2) were densely packed along a narrow (70μm) and thin (20μm) implantable shank using integrated CMOS. With twice the number of electrodes compared to state-of-the-art neural probes [2], our design achieves the highest electrode count in a single shank reported so far.

Time multiplexed active neural probe with 678 parallel recording sites

We present a high density CMOS neural probe with active electrodes (pixels), consisting of dedicated in-situ circuits for signal source amplification. The complete probe contains 1356 neuron sized (20×20 μm2) pixels densely packed on a 50 μm thick, 100 μm wide and 8 mm long shank. It allows simultaneous high-performance recording from 678 electrodes and a possibility to simultaneously observe all of the 1356 electrodes with increased noise. This considerably surpasses the state of the art active neural probes in electrode count and flexibility. The measured action potential band noise is 12.4 μVrms, with just 3 μW power dissipation per electrode amplifier and 45 μW per channel (including data transmission).

Why not record from every channel with a CMOS scanning probe

Neural recording devices normally require one output connection for each electrode. This constrains the number of electrodes that can be accommodated by the thin shafts of implantable probes. Sharing a single output connection between multiple electrodes relaxes this constraint and permits designs of ultra-high density neural probes. Here we report the design and in vivo validation of such a device, a complementary metal-oxide-semiconductor (CMOS) scanning probe with 1344 electrodes and 12 reference electrodes along an 8.1 mm × 100 μm × 50 μm shaft; the outcome of the European research project NeuroSeeker. This technology presented new challenges for data management and visualization, and we also report new methods addressing these challenges developed within NeuroSeeker. Scanning CMOS technology allows the fabrication of much smaller, denser electrode arrays. To help design electrode configurations for future probes, several recordings from many different brain regions were made with an ultra-dense passive probe fabricated using CMOS process. All datasets are available online.

Intraneural active probe for bidirectional peripheral nerve interface

Advanced bionic prosthetics that can restore both the motor functionality and sensory perception of an amputee, require high-resolution recording and stimulation interfaces targeting the peripheral nervous system (PNS). To provide high nerve fiber selectivity, we propose a low-noise (3.67μVrms) low-power (2.24mW) and high-density CMOS microelectrode probe for intra-neural implantation. The probe is composed of two ICs, encapsulated in a biocompatible and hermetic package, each featuring 64 recording and 16 stimulation electrodes. A backend IC digitizes the recorded signals at 31.25kS/s and provides spike detection.

Analysis of passive charge balancing for safe current-mode neural stimulation

Charge balancing has been often considered as one of the most critical requirement for neural stimulation circuits. Over the years several solutions have been proposed to precisely balance the charge transferred to the tissue during anodic and cathodic phases. Elaborate dynamic current sources/sinks with improved matching, and feedback loops have been proposed with a penalty on circuit complexity, area or power consumption. Here we review the dominant assumptions in safe stimulation protocols, and derive mathematical models to determine the effectiveness of passive charge balancing in a typical application scenario.