DNA sequencing plays a significant role in modern human health diagnosis. It enables studies of metagenomics, genetic disorders, diseases, and genomic medicine.  For optical sequencing, a laser source, an optical filter and a Charge-Coupled Device (CCD)-based image sensor are employed. DNA sequence information is converted to light intensity through the use of fluorescence dyes. However, the involved optical imaging system is bulky and expensive that only hospitals and research centers can afford. In this paper, a miniaturized CMOS-image-sensor (CIS) based fluorescence detector is proposed to deal with these challenges. Firstly, semiconductor quantum dots (QDs) are employed. Compared to traditional organic fluorescence labels, QDs present higher quantum yields and longer life times. In this way, light intensity is enhanced from the source. Secondly, an on-chip optical filter is designed to reject the background excitation light and pass through the emission fluorescent light. Simulation results show that the 400~450nm excitation light is almost 100% absorbed and the 750~850nm fluorescent light is highly transparent. The transmission signal-to-noise ratio (SNR) between 400nm and 800nm can reach 64dB. Lastly, a 1-pA resolution Capacitive Transimpedance Amplifier (CTIA) with Correlated Double Sampling (CDS) are employed to realize a high-sensitivity readout circuit. Therefore, a highly CMOS integrated fluorescence imaging system can effectively reduce the size and cost of sequencing, which is a promising technique for personalized sequencing.