A multi-channel mixed-signal full-customized CMOS integrated biopotential sensor chip and microcontroller based electronic system have been developed for in vitro extracellular recording of neural signals. The multi-site planar microelectrode array sensors for simultaneous neural signal recording have been designed and prototyped with on-chip fully integrated analog signal processing circuitry and control system. The biosensor system is built with hierarchical modules that incorporate microelectrode electrophysiological sensors, analog signal buffers configured with two-stage amplifier, gain providing amplifiers based on operational transconductance amplifier (OTA) with capacitive feedback and digital logic and interface units including clock generation and time division multiplexing control circuitry. The prototype IC was fabricated by MOSIS using AMI C5 0.5 mu m, double poly, triple metal layer CMOS technology. The electroless gold plating process is used to replace the aluminum material obtained from the standard CMOS process with biocompatible metal gold in the planar microelectrode array sensors to prevent cell poisoning and undesirable electrochemical corrosion. The post-CMOS processing and packaging techniques applied to the biosensor chip promotes biocompatibility and stability in the aqueous cell culture environment. A microcontroller based electronic system interfacing the biosensor IC with a client PC for the post processing of the action potential signals sensed by the biopotential sensor chip was also developed. The biosensor has been tested electrically in the presence of electrolyte environment and is shown to provide a satisfactory signal-to-noise ratio for neural signals with amplitudes in the range of 600 mu V-2mV and frequencies in the range of 100 Hz - 10 kHz. Biological example in vitro recordings conducted with neurons from Aplysia californica are shown in this research work, which proves the full functionality in neural recording of the biosensor chip incorporated with the interfacing electronic system based on 32-bit Motorola ColdFire MCF5307 RISC processor. On-chip amplification and time division multiplexing techniques of the multi-channel biosensor chip allow the large-scale simultaneous recording of biological activities of neurons.