A neuronal signal detecting circuit and a neuronal signal stimulating circuit designed for a monolithic integrated MEA（micro-electrode array） system are described. As a basic cell of the circuits, an OPA（ operational amplifier） is designed with low power, low noise, small size and high gain. The detecting circuit has a chip area of 290 μm × 400 μm, a power dissipation of 2.02 mW, an equivalent input noise of 17.72 nV/ Hz, a gain of 60. 5 dB, and an output voltage from - 2. 48 to ＋ 2. 5 V. The stimulating circuit has a chip area of 130 μm × 290 μm, a power dissipation of 740 μW, and an output voltage from - 2. 5 to 2. 04 V. The parameters show that two circuits are suitable for a monolithic integrated MEA system. The detecting circuit and MEA have been fabricated. The test results show that the detecting circuit works well.
A stable CMOS low drop-out regulator without an off-chip capacitor for system-on-chip application is presen- ted. By using an on-chip pole splitting technique and an on-chip pole-zero canceling technique, high stability is achieved without an off-chip capacitor. The chip was implemented in CSMC＇s 0.5μm CMOS technology and the die area is 600μm×480μm. The error of the output voltage due to line variation is less than -＋ 0.21% ,and the quiescent current is 39.8μA. The power supply rejection ratio at 100kHz is -33.9dB, and the output noise spectral densities at 100Hz and 100kHz are 1.65 and 0.89μV √Hz, respectively.
A microelectrode array（MEA） is presented, which is composed of 60 independent electrodes with 59 working ones and one reference one, and they are divided into 30 pairs. Except for the reference electrode, each pair consists of one stimulating electrode and one recording electrode. Supported by the peripheral circuits, four electrode states to study the bioelectrical signal of biological tissue or slice cultured in-vitro on the surface of the electrodes can be realized through each pair of electrodes. The four electrode states are stimulation, recording, stimulation and recording simultaneously, and isolation. The state of each pair of working electrodes can be arbitrarily controlled according to actual needs. The MEAs are fabricated in printed circuit board （PCB） technology. The total area of the PCB-based MEA is 49 mm × 49 mm. The impedance measurement of MEA is carried out in 0.9% sodium chloride solution at room temperature by means of 2-point measurements with an Agilent LCR meter, and the test signal for the impedance measurement is sinusoidal （AC voltage 50 mV, sweeping frequency 20 Hz to 10 kHz）. The electrode impedance is between 200 and 3 kΩ while the frequency is between 500 and 1 000 Hz. The electrode impedance magnitude is inversely proportional to the frequency. Experiments of toad sciatic nerve in-vitro stimulation and recording and signal regeneration between isolated toad sciatic nerves are carried out on the PCB-based MEA. The results show that the MEA can be used for bioelectrical signal stimulation, recording, stimulation and recording simultaneously, and isolation of biological tissues or slices in-vitro.
A microelectronic circuit is used to regenerate the neural signals between the proximal end and the distal end of an injured nerve.An experimental scheme is designed and carried out to verify the feasibility of the so-called microelectronic neural bridge（MNB）.The sciatic signals of the source spinal toad which are evoked by chemical stimuli are used as source signals to stimulate the sciatic of the controlled spinal toad.The sciatic nerve signals of the source spinal toad,the regenerated sciatic signals in the controlled spinal toad,and the resulting electromyography（EMG）signals associated with the gastrocnemius muscle movements of the controlled spinal toad are displayed and recorded by an oscilloscope.By analyzing the coherence between the source sciatic nerve signals and the regenerated sciatic nerve signals and the coherence between the regenerated nerve signals and the EMG signals,it is proved that the regenerated sciatic nerve signals have a relationship with the source sciatic nerve signals and control shrinkage of the leg of the controlled toad.
According to the feature of neural signals,a micro-electronic neural bridge（MENB）has been designed. It consists of two electrode arrays for neural signal detection and functional electrical stimulation（FES）,and a microelectronic circuit for signal amplifying,processing,and FES driving.The core of the system is realized in 0.5-μm CMOS technology and used in animal experiments.A special experimental strategy has been designed to demonstrate the feasibility of the system.With the help of the MENB,the withdrawal reflex function of the left/right leg of one spinal toad has been rebuilt in the corresponding leg of another spinal toad.According to the coherence analysis between the source and regenerated neural signals,the controlled spinal toad＇s sciatic nerve signal is delayed by 0.72 ms in relation to the sciatic nerve signal of the source spinal toad and the cross-correlation function reaches a value of 0.73.This shows that the regenerated signal is correlated with the source sciatic signal significantly and the neural activities involved in reflex function have been regenerated.The experiment demonstrates that the MENB is useful in rebuilding the neural function between nerves of different bodies.
Based on the 4-channel neural signal regeneration system which is realized by using discrete devices and successfully used for in-vivo experiments on rats and rabbits, a single channel neural signal regeneration integrated circuit （IC）is designed and realized in CSMC ＇ s 0. 6 μm CMOS （ complementary metal-oxide-semiconductor transistor ） technology. The IC consists of a neural signal detection circuit with an adjustable gain, a buffer, and a function electrical stimulation （FES） circuit. The neural signal regenerating IC occupies a die area of 1.42 mm × 1.34 mm. Under a dual supply voltage of ±2. 5 V, the DC power consumption is less than 10 mW. The on-wafer measurement results are as follows： the output resistor is 118 ml）, the 3 dB bandwidth is greater than 30 kHz, and the gain can be variable from 50 to 90 dB. The circuit is used for in-vivo experiments on the rat＇ s sciatic nerve as well as on the spinal cord with the cuff type electrode array and the twin-needle electrode. The neural signal is successfully regenerated both on a rat＇ s sciatic nerve bundle and on the spinal cord.
