Noninvasive sensing of blood glucose based on near-infrared (NIR) spectroscopy is a research hotspot in the biomedical field. However, its accuracy is severely limited by the weak specific signal of glucose and the strong background variations caused by other constituents in the blood, the measuring instrument, and the environment. In this paper, special source–detector distances, defined as the floating reference position, are used to conduct relative measurements and correct for background variations. These floating reference positions are chosen so that the diffuse reflectance is not sensitive to the change in glucose concentration due to the combined effects of absorption and scattering. Nine 10% intralipid samples with glucose concentrations in the range of 1000–5000 mg dL–1 at an interval of 500 mg dL–1 were prepared. Using a custom-built, continuously moving, spatially resolving, double-fiber measurement system with a superluminescent diode (SLD) as the light source, the diffuse reflectance of intralipid samples containing glucose under different source–detector distances (0.2–5 mm, with intervals of 0.2 mm) were collected. Then, a correlation analysis between the spectra and the glucose concentration was carried out to determine the floating reference position and the optimal measuring position. The signal in the floating reference position was used to correct the background variation because it contains the same systematic drift and interference as the signal in the optimal measuring position. The results showed that the correlation between the diffuse reflectance and the glucose concentration was increased significantly compared with traditional correction by subtracting the nearest spectrum of pure 10% intralipid solution. The correlation between the diffuse reflectance and the concentration of glucose is significantly increased, which indicated that the combination of the correlation analysis and a floating reference is able to eliminate the influence of background variations.
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