%X This article is clearly presenting the development of a biosensor for human factor IX (FIX) to diagnose the blood clotting deficiency, a so-called �Royal disease� using an interdigitated electrode (IDE) with the zinc oxide surface modification. Gold nano-urchins (GNUs) with 60 nm in diameter was integrated into a streptavidin-biotinylated aptamer strategy to enhance the active surface area. Two different comparative studies have been done to validate the system to be practiced in the current work holds with a higher capability for the high-performance sense. Whereby, the presence and absence of GNUs in the aptasensing system for FIX interaction were investigated using the amperometric measurement, using a linear sweep voltage of 0�2 V at 0.01 V step voltage. The detection limit was 6 pM based on 3� calculation when GNUs integrated aptamer assay was utilized for FIX detection, which shows 8 folds sensitivity enhancement comparing the condition in the absence of GNU and 50 folds higher than sensitive radio-isotope and surface plasmon resonance assays. Albeit, the surface and molecular characterizations were well demonstrated by scanning electron microscopy, atomic force microscopy, 3D nano-profilometry and further supports were rendered by UV�Vis spectroscopy and Enzyme-linked apta-sorbent assay (ELASA). Furthermore, the spiking experiment was done by FIX-spikes in human blood serum in order to demonstrate the stability with a higher non-fouling. © 2019 Elsevier B.V. %K Atomic force microscopy; Gold; II-VI semiconductors; Proteins; Scanning electron microscopy; Surface plasmon resonance; Surface treatment; Zinc oxide, Amperometry; Aptamers; ELASA; Factor ix; Gold nano, Blood, blood clotting factor 9; gold nanoparticle; radioisotope; zinc oxide; aptamer; blood clotting factor; blood clotting factor 9; gold; streptavidin, Article; atomic force microscopy; biotinylation; chemical modification; electric potential; enzyme linked immunosorbent assay; hemophilia; intermethod comparison; limit of detection; process development; profilometry; prognosis; protein binding; scanning electron microscopy; sensitivity analysis; surface area; surface plasmon resonance; ultraviolet visible spectroscopy; blood clotting; chemistry; electrode; genetic procedures; genetics; human; isolation and purification, Aptamers, Nucleotide; Biosensing Techniques; Blood Coagulation; Blood Coagulation Factors; Electrodes; Factor IX; Gold; Humans; Limit of Detection; Prognosis; Streptavidin; Surface Plasmon Resonance %R 10.1016/j.bios.2019.02.006 %D 2019 %J Biosensors and Bioelectronics %L scholars11631 %O cited By 65 %I Elsevier Ltd %A I. Letchumanan %A S.C.B. Gopinath %A M.K. Md Arshad %A P. Anbu %A T. Lakshmipriya %V 131 %T Gold nano-urchin integrated label-free amperometric aptasensing human blood clotting factor IX: A prognosticative approach for �Royal disease� %P 128-135