Telomerase has attracted much attention as a universal cancer biomarker because telomerase is overexpressed in more than 85% of human cancer cells while suppressed in normal somatic cells. Since a strong association exists between telomerase activity and human cancers, the development of effective telomerase activity assay is critically important. Here, a nanogaprich Au nanowire (NW) surface-enhanced Raman scattering (SERS) sensor is reported for detection of telomerase activity in various cancer cells and tissues. The nanogap-rich Au NWs are 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. This sensor enables us to detect telomerase activity from various cancer cell lines with a detection limit of 0.2 cancer cells mL −1 . Importantly, the nanogap-rich Au NW sensor can diagnose gastric and breast cancer tissues accurately. The nanogap-rich Au NW sensors show strong SERS signals only in the presence of tumor tissues excised from 16 tumorbearing mice, while negligible signals in the presence of heated tumor tissues or normal tissues. It is anticipated that nanogap-rich Au NW SERS sensors can be used for a universal cancer diagnosis and further biomedical applications including a diverse biomarker sensing.

Atomically flat surfaces of single-crystalline Au nanoplates can maximize the functionality of biomolecules, thus realizing extremely high-performance biosensors. Here, we report both highly specific and supersensitive detection of C-reactive protein (CRP) by employing atomically flat Au nanoplates. CRP is a protein biomarker for inflammation and infection and can be used as a predictive or prognostic marker for various cardiovascular diseases. To maximize the binding capacity for CRP, we carefully optimized the Au nanoplate-Cys3-protein G-anti-CRP structure by observing atomic force microscopy (AFM) images. The optimally anti-CRP-immobilized Au nanoplates allowed extremely specific detection of CRP at the attomolar level. To confirm the binding of CRP onto the Au nanoplate, we assembled Au nanoparticles (NPs) onto the CRP-captured Au nanoplate by sandwich immunoreaction and obtained surface-enhanced Raman scattering (SERS) spectra and scanning electron microscopy (SEM) images. Both the SERS and SEM results showed that we completely eliminated the nonspecific binding of Au NPs onto the optimally anti-CRP-immobilized Au nanoplate. Compared with the anti-CRP-immobilized rough Au film and the randomly anti-CRP-attached Au nanoplate, the optimally anti-CRP-immobilized Au nanoplate provided a highly improved detection limit of 10–17 M. In this study, it was validated that ultraclean and ultraflat Au nanoplates can maximize the sensing capability of CRP. We expect that these Au nanoplates will enable the feasible detection of many important biomarkers with high specificity and high sensitivity.

We report the surfactant-free vapor-phase synthesis of atomically flat and ultraclean gold nanoplates. These gold nanoplates can offer optimally functional surfaces through the immobilization of molecules without unspecific adsorption and defect, which could be quite valuable for diverse applications including biomedical sensing, plasmonics, molecular electronics, electrochemistry, etc. The ultraflat, ultraclean, and single-crystalline nanostructures, including gold nanoparticles (NPs), gold nanowires (NWs), gold nanobelts, and gold nanoplates, are stereoepitaxially grown on a substrate with a specific orientation. Moreover, the nanostructures can be selectively synthesized by experimental conditions and locations of the substrate. The geometry and orientation of the nanostructures show strong correlations, suggesting a growth process of seed NPs → NWs → nanobelts → nanoplates. This synthetic process can be explained by the mechanism in which the height-to-width ratio of gold nanostructures is determined by the ratio of the atom-supply rate by direct impingement to the atom-supply rate by surface diffusion. We finely tuned the shapes (NPs, NWs, nanobelts, or nanoplates) and sizes (from several micrometers to hundreds of micrometers) of the gold nanostructures by adjusting the deposition flux. Crucially, the surfactant-free and atomically flat gold nanoplates could be optimally bioactive surfaces. We substantially decreased the nonspecific binding of avidin by immobilizing the biotinylated molecules onto the gold nanoplates. Compared with thermally deposited gold films, the single-crystalline gold nanoplates showed a 100 times lower detection limit in the recognition of the biotin−avidin interaction. We anticipate that the gold nanoplates will bring us one-step closer to the realization of ideal biomolecular sensors because the several bioactive gold surfaces can be prepared by immobilizing various biological molecules onto the gold nanoplates.

Influenza viruses cause respiratory infection, spread through respiratory secretions, and are shed into the nasal secretion and saliva specimens. Therefore, nasal fluid and saliva are effective clinical samples for the diagnosis of influenza virus-infected patients. Although several methods have been developed to detect various types of influenza viruses, approaches for detecting mutant influenza viruses in clinical samples are rarely reported. Herein, we report for the first time a surface-enhanced Raman scattering (SERS)-based sensing platform for oseltamivir-resistant pandemic H1N1 (pH1N1) virus detection in human nasal fluid and saliva. By combining SERS-active urchin Au nanoparticles and oseltamivir hexylthiol, an excellent receptor for the pH1N1/ H275Y mutant virus, we detected the pH1N1/H275Y virus specifically and sensitively in human saliva and nasal fluid samples. Considering that the current influenza virus infection testing methods do not provide information on the antiviral drug resistance of the virus, the proposed SERS-based diagnostic test for the oseltamivir-resistant virus will inform clinical decisions about the treatment of influenza virus infections, avoiding the unnecessary prescription of ineffective drugs and greatly improving therapy.

Single-crystalline β-Ag2Se nanostructures, a new class of 3D topological insulators (TIs), were synthesized using the chemical vapor transport method. The topological surface states were verified by measuring electronic transport properties including the weak antilocalization effect, Aharonov-Bohm oscillations, and Shubnikov-de Haas oscillations. First-principles band calculations revealed that the band inversion in β-Ag2Se is caused by strong spin-orbit coupling and Ag-Se bonding hybridization. These investigations provide evidence of nontrivial surface state about β-Ag2Se TIs that have anisotropic Dirac cones.

To prevent the global transmission of mutant viruses and minimize the damage caused by mutant virus infection, the accurate identification of newly emerged mutant viruses should be a priority. The key problem in mutant virus identification is that the selective detection of a mutant virus in the biological environment, where small amounts of mutant virus and copious amounts of wild-type virus coexist, is difficult. Herein, we report specific and ultrasensitive detection of oseltamivir-resistant (pH1N1/H275Y mutant) virus using functional Au nanoparticles (NPs). The functional Au NPs were prepared by modifying the surfaces of Au NPs with oseltamivir hexylthiol (OHT) and malachite green isothiocyanate (MGITC) simultaneously. OHT is an excellent receptor for the pH1N1/H275Y mutant virus because it has a 250-fold higher binding affinity for the pH1N1/H275Y mutant virus than for the wild-type virus. MGITC is a Raman reporter that provides a distinctive surface-enhanced Raman scattering (SERS) signal. The SERS signal of MGITC on Au NPs allows us to detect pH1N1/H275Y mutant viruses sensitively and quantitatively. The functional Au NPs enable naked-eye and SERS dual-mode detection of mutant viruses. Only in the presence of the pH1N1/H275Y mutant virus, the functional Au NPs aggregate, and the color of the NPs changes from red to purple. This allows us to detect mutant viruses with the naked eye. Furthermore, the aggregated Au NPs can provide strong SERS signals of MGITC. By measuring the SERS signals, we could detect the pH1N1/H275Y mutant virus with a detection limit of 10 PFU. Importantly, the pH1N1/H275Y mutant virus could be detected by using the functional Au NPs even in a mixture of mutant and wild-type viruses with a ratio of 1/100. This result suggests that the present method might be employed for the diagnosis of oseltamivir-resistant virus and for further research, including mutant virus analysis and drug development.

We report facile and sensitive influenza virus detection method using surface-enhanced Raman scattering antibody probes.

Ovarian cancer is the fifth leading cause of cancer-related deaths among women. In particular, it is a high cause of mortality among women in industrialized countries. Human epididymis protein 4 (HE4) has recently emerged as a serological biomarker for the diagnosis of ovarian cancer. Herein, we report the ultrasensitive detection of HE4 using a gold (Au) nanoplate (NPl)-based surface-enhanced Raman scattering (SERS) immunoassay, wherein a capture antibody-immobilized Au NPl acts as an immune substrate and detection antibody-immobilized Au nanoparticles (NPs) serve as immunoprobes. The presence of the target biomarker (HE4) results in the formation of a sandwich structure of Au NPls and NPs, providing strong SERS signals. The developed method allows us to detect HE4 at low concentrations of 10 -17 M. The selective detection of HE4 was verified using the Au NPl SERS immunoassay. We anticipate that the current approach could be helpful for the early diagnosis of ovarian cancer and eventually applied for diverse biomarker detection.