Abstract: A method of using Neutrilized DNA (N-DNA) as a surface probe for a high throughput detection platform is disclosed. FET and SPRi are used as high throughput detection platforms to demonstrate that the N-DNA surface probe produces good results and enhances detection sensitivity. The N-DNA modifies the charged oxygen ions (O?) on the phosphate backbone through methylation, ethylation, propylation, or alkylation, so that the backbone is not charged after this modification to increase the hybridization efficiency, sensitivity and to make the signal more clear.