The ability to efficiently detect trace biomarkers of disease in whole blood remains a significant challenge. Multi-mode signals - electrochemical, fluorescence, and ultraviolet-visible spectroscopy (Uv-vis spectra) have self-correction capabilities that can overcome the interference of experimental and environmental factors on the output. Based on the "functionalized UiO-67 MOF", biomorphic inspired the octopus-three mode aptamer sensor (OTMBapt sensor) was constructed by imitating the structure of octopus without immobilization, labes and enzymes. Ultra-sensitive and high-precision biosensor detection of HER2 in human whole blood was achieved by using Uv-vis, fluorescence and electrochemical homogeneous techniques. This sensor uses a functionalized UiO-67 (aptamer@UiO-67) as the "octopus body". Due to targeting HER2, the HER2 aptamer is looped, and as a result of the folded aptamer, a large number of " tentacles " are extended, resulting in the ability to adsorb methylene blue (MB) molecules in a homogeneous solution. Finally, the active molecule MB is electrically doped in the folding aptamer structure to form a "sucker". This will enrich and adsorb negatively charged MB molecules onto the ITO surface, leading to the enhanced electrochemical, fluorescence and Uv-vis signal intensity. A detection time of 10 min, limit of detection (LOD) is 0.2 fg/mL with the linear range of 0.3–1000 pg/mL.