Development of gold nanowire based surface-enhanced raman scattering sensor for biochemical application

Abstract

Surface-enhanced Raman scattering (SERS) is a fascinating phenomenon that increases Raman signals from molecules located in metallic nanostructure by a factor of $10^6$ or more. Since its discovery in the 1970s, the interest and use of SERS have grown dramatically due to its high sensitivity and selectivity for detecting molecules. The field of SERS has now developed into a mature field and with the advent of state-of-the-art precise nanofabrication methods, single molecule detection become possible. The application of SERS has moved from physics to material science, chemistry, and more recently to biochemical applications. In this dissertation, we present the works on Au nanowires (NWs) based SERS sensors for various biochemical applications. The single-crystalline Au NW synthesized in vapor phase without surfactants have atomically smooth surface. The use of Au NWs is highly advantageous for the SERS based detection of biochemical species because their well-defined geometric architecture provides reliable reproducibility, time stability and excellent sensitivity. The detailed description covered in chapters 2-6 are as follows. MicroRNAs (miRNAs) are emerging new biomarkers for many human diseases. To fully employ miRNAs as biomarkers for clinical diagnosis, it is most desirable to accurately determine the expression patterns of miRNAs. In chapter 2, an ultra-specific detection method of miRNAs with zeptomole sensitivity is reported by applying bi-temperature hybridizations on single-crystalline PNI sensors. This method shows near-perfect accuracy of SNPs and a very low detection limit of 100 am without any amplification or labeling steps. Furthermore, multiplex sensing capability and wide dynamic ranges of this method allows reliable observation of the expression patterns of miRNAs extracted from human tissues. The PNI sensor offers combination of ultra-specificity and zeptomole sensitivity while requiring two steps of hybridization between short oligonucleotides, which could present the best set of features for optimum miRNA sensing method. In chapter 3, we report a nanogap-rich Au NW SERS sensor for detection of telomerase activity in various cancer cells and tissues. The nanogap-rich Au NWs were constructed by deposition of nanoparticles on single-crystalline Au NWs and provided highly reproducible SERS spectra. The telomeric substrate (TS) primer-attached nanogap-rich Au NWs can detect telomerase activity through SERS measurement after the elongation of TS primers, folding into G-quadruplex structures, and intercalation of methylene blue. The nanogap-rich Au NW sensors showed strong SERS signals only in the presence of tumor tissues excised from 16 tumor-bearing mice, while negligible signals in the presence of heated tumor tissues or normal tissues. We anticipate that nanogap-rich Au NW SERS sensors can be used for a universal cancer diagnosis and further biomedical applications including a diverse biomarker sensing. In chapter 4, we report an extremely simple method for transferring single-crystalline Au NWs onto Au substrates for the large-scale fabrication of sensitive, reproducible, and highly stable SERS sensors. Vertically grown Au NWs on a sapphire substrate can be horizontally transferred onto an Au substrate via a simple attachment and detachment process, and the resulting Au NWs on the Au substrate are SERS active platforms. By combining Au NW SERS sensors with DNA aptamer, we successfully detected human α-thrombin as well as $Pb^{2+}$ and $Hg^{2+}$ ions in a single step. Because Au NWs can be routinely transferred onto Au substrates and because the resultant Au NW SERS sensors are highly stable and provide with high sensitivity and reproducibility of detection, these sensors hold potential for practical use in biochemical sensing. Uranium is an essential raw material in nuclear energy generation

however, its use raises concerns about the possibility of severe damage to human health and the natural environment. In chapter 5, we report an ultrasensitive ${UO_2}^{2+}$ detection method in natural water that uses a plasmonic NW interstice (PNI) sensor combined with a DNAzyme-cleaved reaction. ${UO_2}^{2+}$ induces the cleavage of DNAzymes into enzyme strands and released strands, which include Raman-active molecules. A PNI sensor can capture the released strands, providing strong surface-enhanced Raman scattering signal. The PNI sensor operates perfectly, even in ${UO_2}^{2+}$-contaminated natural water samples. This suggests the potential usefulness of a PNI sensor in practical ${UO_2}^{2+}$-sensing applications. Developing a well-defined nanostructure that can provide reliable SERS signals is quite important for the practical application of SERS sensors. In chapter 6, we report here a novel single NW on graphene SNOG structure as an efficient, reproducible, and stable SERS-active platform. Au NWs having a well-defined geometry on a monolayer graphene-coated metal film can form a well-defined, continuous nanogap structure that provides reproducible and stable SERS signals. The in-NW reproducibility of the SNOG platform was verified by 2D Raman mapping and the NW-to-NW reproducibility was demonstrated by the cumulative curves of 32 SERS spectra. Furthermore, the SNOG platform showed significantly improved oxidation immunity. We anticipate that SNOG platforms will be appropriate for practical biological and chemical sensor applications that demand reproducible, stable, and strong signal production.