Institute of Nanotechnology (INT), Karlsruhe Institute of Technology (KIT), Hermann-von-Helmholtz Platz 1, 76344, Eggenstein-Leopoldshafen, Germany.
Karlsruhe Nano Micro Facility (KNMFi), Karlsruhe Institute of Technology (KIT), Hermann-von-Helmholtz Platz 1, 76344, Eggenstein-Leopoldshafen, Germany.
Nat Commun. 2023 Jan 31;14(1):518. doi: 10.1038/s41467-023-36057-3.
Sensing small biomolecules in biofluids remains challenging for many optical chemosensors based on supramolecular host-guest interactions due to adverse interplays with salts, proteins, and other biofluid components. Instead of following the established strategy of developing alternative synthetic binders with improved affinities and selectivity, we report a molecular engineering approach that addresses this biofluid challenge. Here we introduce a cucurbit[8]uril-based rotaxane chemosensor feasible for sensing the health-relevant biomarker tryptophan at physiologically relevant concentrations, even in protein- and lipid-containing human blood serum and urine. Moreover, this chemosensor enables emission-based high-throughput screening in a microwell plate format and can be used for label-free enzymatic reaction monitoring and chirality sensing. Printed sensor chips with surface-immobilized rotaxane-microarrays are used for fluorescence microscopy imaging of tryptophan. Our system overcomes the limitations of current supramolecular host-guest chemosensors and will foster future applications of supramolecular sensors for molecular diagnostics.
由于与盐、蛋白质和其他生物流体成分的不利相互作用，基于超分子主体-客体相互作用的许多光学化学传感器在感测生物流体中的小分子生物分子方面仍然具有挑战性。我们没有遵循开发具有改进亲和力和选择性的替代合成配体的既定策略，而是报告了一种分子工程方法来解决这个生物流体挑战。在这里，我们引入了一种基于葫芦[8]脲的轮烷化学传感器，可用于感测与健康相关的生物标志物色氨酸，即使在含有蛋白质和脂质的人血清和尿液中也是如此。此外，这种化学传感器能够在微孔板格式中进行基于发射的高通量筛选，并且可用于无标记酶反应监测和手性传感。带有表面固定化轮烷微阵列的印刷传感器芯片可用于色氨酸的荧光显微镜成像。我们的系统克服了当前超分子主体-客体化学传感器的局限性，并将为用于分子诊断的超分子传感器的未来应用铺平道路。
