Label-free optical detection of insulin would allow in vitro assessment of pancreatic cell functions in their natural state and expedite diabetes-related clinical research and treatment; however, no existing method has met these criteria at physiological concentrations. Using spatially uniform 3D gold-nanoparticle sensors, we have demonstrated surface-enhanced Raman sensing of insulin in the secretions from human pancreatic islets under low and high glucose environments without the use of labels such as antibodies or aptamers. Label-free measurements of the islet secretions showed excellent correlation among the ambient glucose levels, secreted insulin concentrations, and measured Raman-emission intensities. When excited at 785 nm, plasmonic hotspots of the densely arranged 3D gold-nanoparticle pillars as well as strong interaction between sulfide linkages of the insulin molecules and the gold nanoparticles produced highly sensitive and reliable insulin measurements down to 100 pM. The sensors exhibited a dynamic range of 100 pM to 50 nM with an estimated detection limit of 35 pM, which covers the reported concentration range of insulin observed in pancreatic cell secretions. The sensitivity of this approach is approximately 4 orders of magnitude greater than previously reported results using label-free optical approaches, and it is much more cost-effective than immunoassay-based insulin detection widely used in clinics and laboratories. These promising results may open up new opportunities for insulin sensing in research and clinical applications.

中文翻译：

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在生理浓度下基于表面增强拉曼光谱的无标记胰岛素检测以分析胰岛表现

胰岛素的无标记光学检测可以在体外进行评估胰腺细胞处于自然状态的功能，并加快糖尿病相关的临床研究和治疗；但是，没有一种现有方法在生理浓度下满足这些标准。使用空间均匀的3D金纳米颗粒传感器，我们已经证明了在低葡萄糖和高葡萄糖环境下，人胰岛分泌物中胰岛素的表面增强拉曼传感，而无需使用诸如抗体或适体的标记。胰岛分泌物的无标记测量结果显示，环境葡萄糖水平，分泌的胰岛素浓度和测量的拉曼发射强度之间具有极好的相关性。在785 nm激发时，密集排列的3D金纳米粒子柱的等离激元热点以及胰岛素分子和金纳米粒子的硫化物键之间的强相互作用产生了高达100 pM的高度灵敏和可靠的胰岛素测量值。这些传感器的动态范围为100 pM至50 nM，估计检测限为35 pM，该范围涵盖了在胰腺细胞分泌物中观察到的报道的胰岛素浓度范围。这种方法的灵敏度比以前报道的使用无标记光学方法的结果高大约4个数量级，并且比在临床和实验室中广泛使用的基于免疫测定的胰岛素检测更具成本效益。这些有希望的结果可能会为研究和临床应用中的胰岛素感测开辟新的机会。