We developed a rapid and accurate biosensor to detect SARS-CoV-2 and distinguish its mutations. Benefitting from a DNA framework-modified ordered interface and a dual signal amplification strategy, our biosensor could detect SARS-CoV-2 with a detection limit down to 10 fM. It performed well on pseudo virus and SARS-CoV-2 RNA standard materials, revealing the potential application in disease diagnosis and spread, in combination with a home-made smartphone.