Quantitative analysis is critical for biological and chemical sensing applications, yet still remains a great challenge in surface-enhanced Raman spectroscopy (SERS). Here we report the development of a novel fractal SERS nanoprobe with robust internal calibration standard and high multiplexing capability for ultrasensitive detection of DNA and microRNA. This fractal SERS nanoprobe consists of a solid Au core of ∼13 nm, an inner hollow gap of ∼1 nm, and a stellate outer shell. The inner hollow gap enables the embedding of Raman tags that can serve as a self-calibrating internal standard to effectively correct the fluctuations of samples and measuring conditions. The outer shell morphology is highly tunable, which provides distinct SERS enhancement and enables a reproducible quantitative measurement of nucleic acids down to femtomolar level. In addition, the flexibility of encoding crosstalk-free Raman tag molecules makes such SERS sensor particularly attractive for multiplexed bioassays. This technique is simple, reliable, and of wide applicability to various genomic screening and diagnostic applications.

定量分析对于生物学和化学传感应用至关重要，但在表面增强拉曼光谱（SERS）中仍然是巨大的挑战。在这里，我们报告一种新型的分形SERS纳米探针的开发，该探针具有强大的内部校准标准和对DNA和microRNA的超灵敏检测的高复用能力。这种分形的SERS纳米探针由〜13 nm的实心Au核，〜1 nm的内部中空间隙和星状外壳组成。内部的中空间隙可以嵌入拉曼标签，这些标签可以用作自校准内标，从而有效地校正样品和测量条件的波动。外壳形态是高度可调的，可提供明显的SERS增强，并能够重复测量定量至低飞摩尔水平的核酸。另外，编码无串扰的拉曼标签分子的灵活性使得这种SERS传感器对于多重生物测定特别有吸引力。该技术简单，可靠，并且广泛适用于各种基因组筛选和诊断应用。