A dual-mode (chemical/optical) CMOS ion-image sensor is demonstrated towards accurate DNA sequencing by integrating the ion-sensitive field-effect transistor (ISFET) with 4-T CMOS image sensor (CIS) pixel fabricated in standard 0.18μm CIS process. With accurate determination of physical locations for microbeads through contact imaging, local pH for one DNA slice attached on the microbead can be obtained with accurate correlation to improve sequencing accuracy from system perspective. Moreover, towards high-throughput large-arrayed sequencing, pixel-to-pixel ISFET threshold voltage mismatch is reduced by correlated double sampling (CDS) readout that supports both image and pH modes. Measurement results show a readout sensitivity of 103.8mV/pH, a fixed-pattern-noise (FPN) reduction from 4% to 0.3%, and a readout speed of 1200 frames/second (fps).