Forty years have passed since the Sanger DNA sequencing technique faced the world. In the past 20 years, the advancement of the sequencing technique has suddenly sped up. This development has shared interests with the semiconductor industry: faster, higher throughput, higher integration level, lower cost. However, it began to slow down from 2015 because the sequencing technique has approached the physics limit. Compared with current technique, sequencing by the DNA intrinsic backbone charge has more potential to further scale down the size of the single sensing device and lower the sequencing cost. The key to this technology is the DNA surface chemistry. In this work, several aspects of the DNA backbone sequencing were studied, and solutions were prepared to further optimize this technique. For example, the silicon nanowire field effect transistor (SiNW FET) is brought up as a good candidate for the backbone sequencing due to its high sensitivity, further scaling down potential and its compatibility to the semiconductor industry. The charge sensing model of SiNW FET was also discussed and the results indicate that the signal generated by the charge variation on the gate can be buffered by the hydroxyl group from the gate surface. Thus, gold is selected as the better gate interface material compared with metal oxide due to the lack of hydroxyl group. To achieve stable signal in the sequencing process, a secondary electrode was introduced to measure the solution potential variation and cancel out the corresponding output noise. To find out the best deposition method of self-assemble monolayer (SAM) for DNA surface chemistry, pH sensing is introduced as a novel verifying method. The atomic layer deposition followed by hydrolysis process is proven to be the best deposition method. To study the surface chemistry for DNA sequencing, several DNA immobilization methods were investigated. To quantitatively examine the DNA surface chemistry process, a novel technique was developed. Complementary DNA strand modified with gold nanoparticle is introduced to the DNA template on the surface and followed by the scanning electron microscopy (SEM) examination. The capability of quantitatively measuring the DNA surface density makes it a perfect examination method for DNA surface chemistry. The second part of the work involves water quality monitoring. The interdigitate electrode array (IDA) sensor can achieve similar sensitivity of total dissolved solid (TDS) as the benchtop conductivity meter. The introduction of the ion selective coating layer to the IDA sensor made it capable of free chlorine detection in the ppm range. The sensing mechanism was discussed and can be used for future modification of the coating layer to achieve better sensitivity and reliability.