Giuseppe Massobrio

A behavioral macromodel of the ISFET in SPICE

Abstract Physico-chemical models of the ISFET (Ion-Sensitive Field-Effect Transistor) were developed by the authors in the past, as SPICE built-in models (BIOSPICE). This approach has some drawbacks, i.e., the need of availability of the program source, a deep knowledge of the code subroutines and structure, and the need of compiling the whole program when a new model has to be implemented or when modifications to the models have to be made. To overcome these drawbacks, a more general and user-friendly approach is presented. It consists of a behavioral macromodel that can be used in conjunction with the most commercial SPICE versions. The behavior of the proposed macromodel has been validated by comparing the results with those obtained by BIOSPICE physico-chemical models and experimental measurements. The proposed macromodel is shown to operate also under subthreshold conditions that can be considered as a promising operating mode for large multisensor ISFET-based integrated systems.

Modeling H/sup +/-sensitive FETs with SPICE

A generalized physical model including two kinds of binding sites is presented on H/sup +/-sensitive ISFET devices. The model results in a set of equations which is introduced into a modified version of the electronic circuit simulation program SPICE. In this way, the effects induced on the device performances by varying several physico-chemical parameters are analyzed. The slope of V/sub out/ versus pH curves is predicted for SiO/sub 2/-, Al/sub 2/O/sub 3/-, and Si/sub 3/N/sub 4/-gate ISFETs. The model is then used to predict the behavior of a hypothetical, partially pH-insensitive (REFET) structure. Finally, the model is utilized to fit the slow response of the Al/sub 2/O/sub 3/-gate ISFET to a pH stop. >

Cultured neurons coupled to microelectrode arrays: circuit models, simulations and experimental data

The purpose of this paper is to characterize the neuron-microelectrode junction, based on the equivalent electric-circuit approach. As a result, recording of action potentials can be simulated with a general-purpose circuit simulation program such as HSPICE. The response of the microelectrode was analyzed as a function of parameters such as sealing resistance and adhesion conditions. The models of the neuron and microelectrode implemented in HSPICE were first described. These models were used to simulate the behavior of the junction between a patch of neuronal membrane (described by the compartmental model) and a microelectrode.

Temperature effects on the ISFET behaviour: simulations and measurements

Abstract Temperature effects on ion-sensitive field-effect transistor (ISFETs) are investigated both from theoretical and experimental point of view. An ISFET model has been implemented into a modified version of SPICE and the effects of temperature on the device behaviour over a user-defined range of pH and temperature have been simulated. The simulated and measured results are then compared and discussed.

Modeling the neuron-carbon nanotube-ISFET junction to investigate the electrophysiological neuronal activity.

Carbon nanotubes arranged in vertical alignment and normal direction to the gate insulator of an ion-sensitive field-effect transistor are proposed as electrical interfaces to neurons, and a model of such a system is developed to simulate and analyze the electrical interactions and the induced extracellular neuronal electrical activity. The results pointed out nanotubes act on the amplitude and the shape of the recorded signals and promote an increase in the efficacy of neuronal signal transmission.

Light-addressable chemical sensors: Modelling and computer simulations

Abstract A light-addressable potentiometric sensor (LAPS) has recently been proposed as a pH sensor. A LAPS description is presented that is suitable for direct applications as a built-in model in circuit-simulation programs, such as SPICE. The model equations describing the LAPS behaviour have been formulated by modelling the electrolyte-insulator interface via site-binding theory, and by modelling, via semiconductor theory, the insulator-semiconductor structure under the photogeneration effects induced by an externally addressed light. Simulation results are presented, focused on the analysis of the detection of transient acidification phenomena.

Multi-program approach for simulating recorded extracellular signals generated by neurons coupled to microelectrode arrays

Purpose of this paper is to present a new tool for characterizing the coupling between neurons and micro-electrode arrays (MEAs), based on a multi-program simulation approach. As a result, recorded extracellular signals generated by networks of neurons coupled to MEAs can be simulated with a combined interaction of modified and developed models implemented in simulation programs such as Spice, Neuron, and Matlab. The proposed approach allows an efficient simulation of the behaviour of the specific neuron-electrode junctions and the simulation of synaptically connected neuronal populations. Models of the neuron, synapse, microelectrode and neuron-electrode junction are presented and comparison between simulation results and multi-site extracellular recordings are shown.

Realistic simulations of neurons by means of an ad hoc modified version of SPICE

This paper describes an ad hoc modified version of the electrical circuit analysis program SPICE, which has been optimized for detailed simulations of the behaviour of neurons. An equivalent-circuit description of the simulation building blocks is provided, and the SPICE modifications are specified. These modifications, in contrast to previous uses of SPICE, allows one to simulate the behaviour of neurons of Hodgkin-Huxley type (excitable membrane) and of postsynaptic membranes without any approximations. Simulation results are reported and compared, both with data previously analysed in the literature by other authors and with experimental data recently obtained by coupling neurons to planar extracellular microelectrodes. Details of the circuit elements used in the simulations are reported. The improvements of our proposed model are discussed in comparison with a previous SPICE-based model described in the literature.

Computer simulations of the responses of passive and active integrated microbiosensors to cell activity

Abstract Detection of cell activity via solid-state microtransducers is a rapidly growing research area. In order to design and test microdevices optimized for specific biological applications, ranging from cell electrophysiology to cell pharmacology, there is an increasing need for systematic computer simulations. As specific examples, the performances of noble-metal microelectrodes, ion-sensitive field-effect transistors (ISFETs) and light-addressable potentiometric sensors (LAPSs) are analysed and discussed by means of computer simulations based on their equivalent circuits.

Interfacing Cultured Neurons to Microtransducers Arrays: A Review of the Neuro-Electronic Junction Models

Microtransducer arrays, both metal microelectrodes and silicon-based devices, are widely used as neural interfaces to measure, extracellularly, the electrophysiological activity of excitable cells. Starting from the pioneering works at the beginning of the 70s, improvements in manufacture methods, materials, and geometrical shape have been made. Nowadays, these devices are routinely used in different experimental conditions (both in vivo and in vitro), and for several applications ranging from basic research in neuroscience to more biomedical oriented applications. However, the use of these micro-devices deeply depends on the nature of the interface (coupling) between the cell membrane and the sensitive active surface of the microtransducer. Thus, many efforts have been oriented to improve coupling conditions. Particularly, in the latest years, two innovations related to the use of carbon nanotubes as interface material and to the development of micro-structures which can be engulfed by the cell membrane have been proposed. In this work, we review what can be simulated by using simple circuital models and what happens at the interface between the sensitive active surface of the microtransducer and the neuronal membrane of in vitro neurons. We finally focus our attention on these two novel technological solutions capable to improve the coupling between neuron and micro-nano transducer.