This paper presents a novel Lab-on-Chip ion imaging platform with programmable gain and array-level offset compensation. An array of 128x128 ISFET pixels are employed as the sensing front end, followed by a two-step column parallel readout circuit. The offset introduced by trapped charge and drift before any chemical event, is stored and fed back to the programmable gain instrumentation amplifier for compensation and signal amplification. A column-parallel 8-bit single slope ADC and 8-bit R-2R DAC are designed to achieve real-time array-level correlated double sampling, which also enables new possibilities to maximize sensitivity using off-chip image processing techniques. The system operates in real-time at a frame rate of up to 1000 fps, with a maximum programmable gain of 1V/ pH. Designed in TSMC0.18BCD process, the chip occupies a die area of 2.3mmx4.5 mm. We anticipate that this work would become a next generation solution for revealing inperceptible ion interactions in various biomedical applications.