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Innovation of ISFET with electrochemical and silicon technology has the advantage of ease of integration with associated signal processing, simplicity, portability and potential on-site screening. ISFET sensor plays a critical role in biomedical instrumentation system. It serves at the front end of instruments in signal acquisition and conditioning circuit, interfacing between the electronic signals and biological signals from physiologic systems being measured. ISFET sensor fabricated with CMOS technology benefits from low cost production, low power and miniaturization enabling for micro-system. OrCAD PSpice facilitates design and testing of circuitry before the costly fabrication, with a library of built in macro models. However, even with its current popularity, macro model for ISFET devices have not yet been made available. Our work contributes to the development of a new macro model for H+ ISFET in PSpice to allow the characterization and parameterization of such devices to be simulated before costly fabrication. Its functionality is verified by comparing its drain current characteristic against that generated from source code from previous work, with discrepancy in sensitivity of ±8% for pH [4 7 10]. It is also found that good performance of H+ ISFET can be achieved with smaller drain voltage which results in faster response, higher sensitivity to chemical input signal, higher reading of drain current, lower cut-off voltage and higher sensitivity in output voltage to change in pH, of 54.79 mV/pH at drain voltage of 0.1V, through simulated experimentation with the newly created macro model.