近日，法国特鲁瓦工程技术大学的Shuwen Zeng及其研究小组与香港中文大学的Ho-Pui Ho等人合作并取得一项新进展。经过不懈努力，他们实现基于原子薄等离子激元纳米材料的单相增强横向位移无标记生物传感。相关研究成果已于2024年1月1日在国际知名学术期刊《光：科学与应用》上发表。

据悉，快速等离子激元生物传感在疾病早期诊断和分子生物学研究中具有重要意义，受到了广泛关注。然而，传统的角度询问等离子激元传感器在无二次放大标记（如等离子激元纳米粒子）的情况下，如何获得更高的灵敏度仍是一个挑战。

为了解决这一问题，该研究团队开发了一种基于相位奇点增强横向位移的等离激元生物传感器。这种奇点表现为共振等离激元基底反射暗点处的突然相位延迟，导致反射光束的巨大位移。本文首次证明了银纳米膜上的原子薄层Ge₂Sb₂Te₅ (GST)是一种新型的相位响应增强等离子激元材料。GST层不仅可以精确地实现单相变化，而且还可以作为活性银纳米膜的保护层。在校准实验中，这种新结构实现了创纪录的最大位移439.3 μm，具有1.72×10⁸nm RIU^-1的超高灵敏度。其检测限限为6.97×10^-7 RIU，位置分辨率为0.12 μm。

此外，对于这种位移询问，研究人员评估了4.54×10¹¹ μm (RIU°)^-1的大优值(FOM)，使痕量生物分子的无标记检测成为可能。在靶向生物传感实验中，优化后的传感器成功检测到最低浓度1×10^-16M的小细胞因子生物标志物(TNF-α和IL-6)。这两种分子是临床诊断中关键的促炎性肿瘤标志物，目前的临床技术无法直接筛选。为了进一步验证本研究传感系统的选择性，研究人员还测量了整合素与精氨酸酰甘氨酸（RGD）肽在不同Mn²⁺离子浓度下的亲和力，范围从1nM到1mM。

附：英文原文

Title: Label-free biosensing with singular-phase-enhanced lateral position shift based on atomically thin plasmonic nanomaterials

Author: Zhu, Shaodi, Jaffiol, Rodolphe, Crunteanu, Aurelian, Vzy, Cyrille, Chan, Sik-To, Yuan, Wu, Ho, Ho-Pui, Zeng, Shuwen

Issue&Volume: 2024-01-01

Abstract: Rapid plasmonic biosensing has attracted wide attention in early disease diagnosis and molecular biology research. However, it was still challenging for conventional angle-interrogating plasmonic sensors to obtain higher sensitivity without secondary amplifying labels such as plasmonic nanoparticles. To address this issue, we developed a plasmonic biosensor based on the enhanced lateral position shift by phase singularity. Such singularity presents as a sudden phase retardation at the dark point of reflection from resonating plasmonic substrate, leading to a giant position shift on reflected beam. Herein, for the first time, the atomically thin layer of Ge₂Sb₂Te₅ (GST) on silver nanofilm was demonstrated as a novel phase-response-enhancing plasmonic material. The GST layer was not only precisely engineered to singularize phase change but also served as a protective layer for active silver nanofilm. This new configuration has achieved a record-breaking largest position shift of 439.3 μm measured in calibration experiments with an ultra-high sensitivity of 1.72×10⁸nm RIU^-1 (refractive index unit). The detection limit was determined to be 6.97×10^-7 RIU with a 0.12 μm position resolution. Besides, a large figure of merit (FOM) of 4.54×10¹¹ μm (RIU°)^-1 was evaluated for such position shift interrogation, enabling the labelfree detection of trace amounts of biomolecules. In targeted biosensing experiments, the optimized sensor has successfully detected small cytokine biomarkers (TNF-α and IL-6) with the lowest concentration of 1×10^-16M. These two molecules are the key proinflammatory cancer markers in clinical diagnosis, which cannot be directly screened by current clinical techniques. To further validate the selectivity of our sensing systems, we also measured the affinity of integrin binding to arginylglycylaspartic acid (RGD) peptide (a key protein interaction in cell adhesion) with different Mn²⁺ ion concentrations, ranging from 1nM to 1mM.

DOI: 10.1038/s41377-023-01345-6

Source: https://www.nature.com/articles/s41377-023-01345-6