CuO nanospheres, synthesized by a simple one-step hydrothermal method, have been applied to modify the glassy carbon (GC) electrode for sensitive nonenzymatic glucose detection. The CuO nanospheres modified electrode, compared to the Nafion modified GC electrode, exhibits an enhanced electrocatalytic property for direct glucose oxidation and shows a fast response and a high sensitivity for the amperometric detection of glucose. It has been determined that the dissolved oxygen is not involved in glucose oxidation and the high concentration of NaCl does not poison the electrode. These results also indicate that CuO nanospheres have great potential application in electrochemical detection.Keywords: Cupric oxide, Nanospheres, Nonenzymatic, Oxidation, Glucose DOI: 10.1002/elan.200804327 Diabetes is a metabolic disorder and a major world health problem. There are over 170 million diabetics worldwide (WHO 2004) and the number is projected to 300 million in 2025, so glucose detection is becoming incredibly important to the patients suffering from diabetes [1,2]. Due to its high sensitivity and selectivity to glucose and stable activity over a broad range of pH [3], glucose oxidase (GOx) has been widely used to construct various amperometric biosensors for glucose detection [1, 4 -12]. However, due to the intrinsic feature of enzymes, GOx-based biosensors suffer from a stability problem [13]. In recent years, considerable attention has been paid to develop enzyme-free electrodes [14 -19]. Precious metals [14,15,17,20], metal alloys [18,21], and metal nanoparticles [16, 22 -24] have been extensively investigated in the development of nonenzymatic glucose sensors. However, these electrodes have drawbacks such as low sensitivity and costliness, and also suffer from the poisoning of chloride ions [15,19,25], thus, their application is greatly limited. Therefore, the development of a cost-effective, sensitive, and reliable enzyme-free glucose sensor is still greatly demanded [13].Cupric oxide (CuO), a p-type semiconductor with a narrow band gap of 1.2 eV, has been studied intensely because of its numerous applications in catalysis, semiconductors, batteries, gas sensors, biosensors, and field transistors [26 -32]. CuO-carbon black modified composite and CuO-coated glass beads have been reported for the detection of glucose, but their application is limited by the tedious fabrication processes [33,34]. With the development of nanotechnology, nanostructured CuO is promising in the development of nonenzymatic glucose sensors because of its highly specific surface area, good electrochemical activity, and the possibility of promoting electron transfer reactions at a lower overpotential. Previous attempts to utilize CuO nanomaterials for the amperometric detection of glucose are limited. Recently Zhuang et al. reported CuO nanowires synthesized on a Cu rod for glucose detection [25]. The developed sensor is elegant and shows an improved sensitivity. However, the synthesis of CuO nanowires is still tedious and involves mu...