In quick response to the deadly viral pandemic such as Ebola virus, SARS, MERS and the most recent COVID-19, diagnostic nucleic acid detection methods are urgently and extensively needed throughout the world. Especially, a fast, minimal reagents consumption assay and portable device would save time and effort, as well as cover more people in risk of the virus. This research aims to develop nucleic acid detection methods on digital microfluidies (DMF) platform for disease diagnostics in need of point-of-care testing. Electrode-wetting based DMF is an emerging technology in the microfluidic field to manipulate individual microliter- to nanoliter-sized droplets on an array of electrodes. Each individual tiny droplet could serve as a vessel of biochemical reaction. Several nucleic acid detection methods are explored on DMF. Among various nucleic acid detection methods, the loop-mediated isothermal amplification (LAMP) stands out for its high amplification efficiency, massive yield and simple product detection. However, challenges remain for its non-specific amplification and the aerosol contamination. To further accelerating reaction rate, polymerase chain reaction (PCR) is a superior option. However, the denaturing temperature near boiling point required in PCR causes a series of issues to be solved, such as the dielectric breakdown, bubbles, the transportation obstruction and the prolonged transportation path. In this context, the feasibility of a newly proposed sequence-specific LAMP assay is studied on DMF platform. The LAMP reaction volume was down to as little as 1 uL of sample with high reproducibility. The detection limit of 10 copies/reaction is comparable with the conventional methods. This LAMP assay achieved sequence- specific results while aerosol contamination is eliminated. Then, to eliminate the need of the bulky fluorescence detection module, a portable LAMP device is implemented. This LAMP assay achieved naked-eye detection with no risk of aerosol contamination. This low-cost, compact device removed the bulky optical system for DNA detection, thus enabling it to be well suited for POC testing. Next in order to develop a fast nucleic acid detection method on the DMF, we have developed a robust DMF system for fast PCR. The reaction volume is down to 0.6 uL, which is 42x lower than the conventional requirement of 25 uL. Bubble generation and dielectric breakdown have been eliminated, supporting over 200 thermal cycles. An ultrafast PCR accomplishing 35 thermal cycles is achieved in 3.2 min, which is the fastest PCR on DMF ever reported. With the effort of developing nucleic acid detection methods, this work provides multiple choices for either a specific, contamination-free and portable LAMP solution or a rapid and robust PCR on the DMF platform. It is envisioned that the entire platform is open for further integration with sample preparation and fluorescence detection towards a micro-total point-of-care system.