Fractal SERS nanoprobes for multiplexed quantitative gene profiling

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.