Almost half of cancer patients are diagnosed late. Early cancer detection in asymptomatic patients will improve the chances of treatment as well as patient outcomes. Lung cancer is the number one cause of cancer deaths for both genders worldwide. Various biomarkers can be used for the early diagnosis of lung cancer, among which circulating tumor DNA (ctDNA) has possibly become the most efficient biomarker. As the most widely used approach, PCR-based assays have the limitations such as long duration, labeling requirement, complicated operation, and high cost. More importantly, PCR-based assay is unable to detect the mutation and methylation degree of ctDNA simultaneously. To overcome these limitations, a novel method was developed for measurement of mutation and methylation of ctDNA, combining the concept of Electrochemical Proximity Assay (ECPA) with our newly developed Multi-Parametric/Multimodal Apparatus System (MPMS). MPMS couples three surface characterization techniques- surface plasmon resonance, electrochemical and fluorescence spectroscopies. The fluorescence intensity indicates the methylation degree, and the current peak implicates the amount of mutated lung cancer ctDNA while the resonance angle change of SPR characterizes the kinetics of each component involved in the assembly of the biosensor. This developed method offers not only high accuracy, sensitivity and specificity, but the information on the kinetics and thermodynamics in the sensor preparation and assembly.