There is an urgent need of label-free technique with low limit of detection (LOD) for biomedical research and early clinical diagnostics. Surface plasmon resonance (SPR) as a label-free approach has been exploited in DNA determination, but the LOD of most SPR sensors is inferior to labeling approaches. A novel approach for SPR biosensing with low LOD was reported in the present study. SPR for long wavelength excitation is theoretically and experimentally demonstrated to possess a high refractive index sensitivity of 11773.93 nm/RIU due to the long decay length of the electromagnetic field near the metal surface, which is optimized by an order of magnitude compared to traditional SPR sensor. Subsequently, self-referencing sensing strategy was employed to eliminate cross-sensitivity problem and further improve sensing accuracy significantly. Finally, we focused on using this sensor to measure DNA hybridization events using graphene oxide-assisted Au nanoparticle conjugates as signal amplification tags. It achieves a large dynamic range of 10⁻¹⁵-10^-11 M and a low LOD of 0.2 fM for target DNA determination. The proposed SPR sensing architecture is technologically simple, highly sensitive and extensively appropriate for existing SPR instrumentation, so it has a great potential for low LOD of various biomolecules.

迫切需要具有低检测限（LOD）的无标记技术，用于生物医学研究和早期临床诊断。表面等离振子共振（SPR）作为一种无标记的方法已被用于DNA测定中，但是大多数SPR传感器的LOD不如标记方法。本研究报道了一种具有低LOD的SPR生物传感的新方法。理论上和实验上证明，用于长波长激发的SPR具有11773.93 nm / RIU的高折射率灵敏度，这是由于金属表面附近电磁场的长衰变长度所致，与传统的SPR传感器相比，其衰减幅度提高了一个数量级。 。随后，采用自参考传感策略消除了交叉敏感问题，并进一步显着提高了传感精度。最后，我们专注于使用该传感器通过使用氧化石墨烯辅助的金纳米颗粒共轭物作为信号放大标签来测量DNA杂交事件。动态范围达到10^-15 -10 ^-11 M和0.2 fM的低LOD用于靶DNA测定。提议的SPR传感体系结构技术简单，高度灵敏，并且广泛适用于现有的SPR仪器，因此对于降低各种生物分子的LOD具有很大的潜力。