Deep-red fluorescence was implemented in this fully injectable, nonenzymatic glucose biosensor design to allow for better light penetration through the skin, particularly for darker skin tones. In this work, a novel method was developed to synthesize Cy5.5 labeled mannose conjugates (Cy5.5-mannobiose, Cy5.5-mannotriose, and Cy5.5-mannotetraose) to act as the fluorescent competing ligand in a competitive binding assay with the protein Concanavalin A acting as the recognition molecule. Using fluorescence anisotropy (FA) data, a computational model was developed to determine optimal concentration ratios of the assay components to allow for sensitive glucose measurements within the physiological range. The model was experimentally validated by measuring the glucose response via FA of the three Cy5.5-labeled mannose conjugates synthesized with Cy5.5-mannotetraose demonstrating the most sensitive response to glucose across the physiological range. The developed method may be broadly applied to a vast range of commercially available fluorescent dyes and opens up opportunities for glucose measurements using nonenzymatic assays.

中文翻译：

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非酶荧光葡萄糖传感测定的计算模型辅助开发


在这种完全可注射的非酶葡萄糖生物传感器设计中实现了深红色荧光，以允许光线更好地穿透皮肤，特别是对于较深的肤色。在这项工作中，开发了一种合成 Cy5.5 标记的甘露糖偶联物（Cy5.5-甘露二糖、Cy5.5-甘露糖三糖和 Cy5.5-甘露糖四糖）的新方法，在竞争性结合测定中充当荧光竞争配体，蛋白质伴刀豆球蛋白 A 作为识别分子。使用荧光各向异性 （FA） 数据，开发了一个计算模型来确定分析组分的最佳浓度比，以便在生理范围内进行敏感的葡萄糖测量。该模型通过测量与 Cy5.5-甘露糖四糖合成的三种 Cy5.5 标记的甘露糖偶联物通过 FA 的葡萄糖反应进行了实验验证，表明在整个生理范围内对葡萄糖的反应最敏感。开发的方法可广泛应用于各种市售荧光染料，并为使用非酶测定法进行葡萄糖测量提供了机会。