Soda Yoshiki, Robinson Kye J, Nussbaum Robin, Bakker Eric
Department of Inorganic, Analytical Chemistry, University of Geneva Quai Ernest-Ansermet 30 1211 Geneva Switzerland
Chem Sci. 2021 Nov 15;12(47):15596-15602. doi: 10.1039/d1sc04930e. eCollection 2021 Dec 8.
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.
用于检测包括鱼精蛋白和肝素在内的聚离子的光学纳米传感器，迄今为止一直依赖于涉及分析物和光学换能器的离子交换反应。不幸的是，由于现有离子载体对聚离子的选择性有限，这种机制在复杂样品基质中受到严重干扰。迄今为止，尚无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。在此，我们基于发现一种“超极化亲脂相”描述了一种新型纳米传感器，在该相中，二壬基萘磺酸（DNNS）使溶剂化显色染料极化的程度甚至比水环境还要高得多。我们发现，只有当DNNS与鱼精蛋白等大型聚离子结合时，有机相的表观极性才会被调节，这与单电荷离子不同，单电荷离子缺乏导致极化DNNS离子分布发生显著变化所需的协同结合。我们的新传感机制允许在换能器不进行离子交换的情况下进行溶剂化显色信号转导。结果是灵敏度和选择性显著提高，首次能够使用光学纳米传感器对人血浆中的鱼精蛋白和肝素进行定量，其结果与当前的金标准分析方法——抗Xa因子测定法相关。
