Paolo Livi

The potential of microelectrode arrays and microelectronics for biomedical research and diagnostics

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

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.

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.

Compact Voltage and Current Stimulation Buffer for High-Density Microelectrode Arrays

We report on a compact (0.02 mm2 ) 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.

Monolithic Integration of a Silicon Nanowire Field-Effect Transistors Array on a Complementary Metal-Oxide Semiconductor Chip for Biochemical Sensor Applications

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.

Compact voltage and current stimulation buffer for high-density microelectrode arrays

The most sophisticated information processing system, the human brain, consists of a huge number of neurons that form part of an intricate network and communicate through electrical and chemical signals via synapses. To elucidate interneuronal communication and network characteristics, it is important to gain bidirectional access (recording and stimulation) to individual neurons and to be able to do closed-loop experiments in cultures. The targeted stimulation of individual neurons, and the subsequent tracking of a signals propagation is a valuable tool to decipher network structures as well as strength and plasticity of involved connections. CMOS-based microelectrode arrays (MEAs) featuring high spatial resolution (subcellular) and low noise provide a wealth of information. Extracellular electrodes ensure cell integrity and long-term recordings; neuronal stimulation is performed by either current or voltage pulses, with typical amplitudes of 0.1 to 1V or 5 to 10µA, and durations of 50 to 900µs [1].

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.

Low power finfet ph-sensor with high-sensitivity voltage readout

Low power n-channel fully depleted local-SOI FinFET integrated sensors have been developed and validated for the amplification of pH sensing signals. A simple architecture with one FinFET connected as depletion-mode load and another one as driving sensor, provides a maximum readout gain of 6.6 V/V with a maximum pH readout sensitivity of 185 mV/pH, at 2 V operation. By comparing the proposed amplifier with a single sensing FinFET the threshold voltage shift readout is shown to be 4.4 times larger. High-k dielectric HfO2 has been used to maximize both sensing and electronic performances. The FinFETs have been fabricated on bulk silicon by a local-SOI technique. FinFET thickness (TFin) and height (HFin) achieved are in the range of 20 nm ≤ T Fin ≤ 40 nm and 65 nm ≤ HFin ≤ 120 nm.

Monolithic system featuring a gold nanowire array on a CMOS chip for biosensing applications

We present a monolithic CMOS-based biosensor system comprising an array of gold nanowires and the signal-conditioning circuitry on the same chip. Different numbers of parallel nanowires have been patterned on the chip via e-beam lithography and lift-off process after the CMOS fabrication. The on-chip circuitry monitors the resistance of the nanowires by applying a constant voltage and measuring the respective current. The analog signal is then digitized on chip and transmitted. The system has been successfully fabricated and tested. I-V curves of the bare nanowires as well as resistance changes for different gold nanowires after applying NaCl solution onto the chip are shown.

A simulation study of N-shell silicon nanowires as biological sensors

Two different silicon nanowire (SiNW) based devices are discussed as potential ion and biological sensors. Three-dimensional TCAD simulations are used to investigate and compare the efficiency of such devices upon applying an external voltage difference of ΔVg = 50 mV. The simulation results presented in this work reveal that an n-doped shell acts as sensitivity booster for uniformly doped SiNWs. It is demonstrated that a 10 nm n-type shell surrounding a p-type core can produce a sensitivity enhancement of more than 50%.