Optical nanosensors for the detection of polyions, including protamine and heparin, have to date relied upon ion-exchange reactions involving an analyte and an optical transducer. Unfortunately, due to the limited selectivity of the available ionophores for polyions, this mechanism has suffered from severe interference in complex sample matrices. To date no optical polyion nanosensors have demonstrated acceptable performance in serum, plasma or blood. Herein we describe a new type of nanosensor based on our discovery of a “hyper-polarizing lipophilic phase” in which dinonylnaphthalenesulfonate (DNNS⁻) polarizes a solvatochromic dye much more than even an aqueous environment. We have found that the apparent polarity of the organic phase is only modulated when DNNS⁻ binds to large polyions such as protamine, unlike singly charged ions that lack the cooperative binding required to cause a significant shift in the distribution of the polarizing DNNS⁻ ions. Our new sensing mechanism allows solvatochromic signal transduction without the transducer undergoing ion exchange. The result is significantly improved sensitivity and selectivity, enabling for the first time the quantification of protamine and heparin in human plasma using optical nanosensors that correlates with the current gold standard analysis method, the anti-Xa factor assay.

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基于溶剂致变色的鱼精蛋白/肝素光学纳米传感器

迄今为止，用于检测聚离子（包括鱼精蛋白和肝素）的光学纳米传感器必须依赖于涉及分析物和光学传感器的离子交换反应。不幸的是，由于可用离子载体对聚离子的选择性有限，这种机制在复杂的样品基质中受到严重干扰。迄今为止，还没有光学聚离子纳米传感器在血清、血浆或血液中表现出可接受的性能。在这里，我们描述了一种基于我们发现的“超极化亲油相”的新型纳米传感器，其中二壬基萘磺酸盐 (DNNS ^- ) 使溶剂致变色染料的极化甚至比水环境中的多得多。我们发现有机相的表观极性仅在 DNNS ^-与大的多聚离子（如鱼精蛋白）结合，不像单电荷离子，单电荷离子缺乏导致极化 DNNS ^-离子分布发生显着变化所需的协同结合。我们的新传感机制允许在传感器不进行离子交换的情况下进行溶剂变色信号转导。结果显着提高了灵敏度和选择性，首次实现了使用与当前金标准分析方法抗 Xa 因子测定相关的光学纳米传感器对人血浆中的鱼精蛋白和肝素进行量化。