A Novel Serum Glucose Quantitative Method Based on a Miniature NMR Analyzer With High Accuracy

A high-accuracy method for serum/blood glucose quantitation was proposed and applied with a benchtop nuclear magnetic resonance (NMR) analyzer, which was developed based on a miniature Halbach magnet. Since the weak signal of trace glucose in serum/blood was difficult to be directly recognized by NMR relaxometry, the related and more sensitive NMR signal response against the original glucose were elicited by adding certain concentrations of glucose oxidase (GOD), ferrous ions (Fe<inline-formula> <tex-math notation="LaTeX">$^{{2}+}{)}$ </tex-math></inline-formula>, and sorbitol. Glucose decomposes under the catalysis of GOD and generates hydrogen peroxide (<inline-formula> <tex-math notation="LaTeX">$\text{H}_{{2}}\text{O}_{{2}}{)}$ </tex-math></inline-formula>, which can oxidize Fe<inline-formula> <tex-math notation="LaTeX">$^{{2}+}$ </tex-math></inline-formula>, resulting in a decrease of NMR relaxation time. Meanwhile, sorbitol can set off a chain reaction between <inline-formula> <tex-math notation="LaTeX">$\text{H}_{{2}}\text{O}_{{2}}$ </tex-math></inline-formula> and Fe<inline-formula> <tex-math notation="LaTeX">$^{{2}+}$ </tex-math></inline-formula>, greatly enhancing the sensitivity and anti-interference of the mapping relationship between glucose concentration and Fe<inline-formula> <tex-math notation="LaTeX">$^{{2}+}$ </tex-math></inline-formula> oxidation ratio. The correlation between glucose concentration and relaxation time was regarded as an empirical model and obtained by polynomial fitting; 283 clinical serum samples were measured to evaluate the quantitation reliability and accuracy of the system. It is finally proved that the average quantitative deviation of our miniature NMR system for 283 serum glucose detection is 5.95 mg/dL [standard deviation (SD) of 4.81 mg/dL] with the coefficient of variation (CV) of repeated detection less than 4%, meeting the requirements of ISO 15197. In conclusion, combined with the miniature NMR analyzer, this novel quantitation method with high-accuracy for serum glucose provides a new reliable and practical tool for detection and community management of diabetes and expected to be further extended to the determination of other biomarkers.