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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.

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 have developed a novel oseltamivir derivative (oseltamivir hexylthiol; OHT) that exhibits a higher binding affinity for Tamiflu-resistant virus (Tamiflu resistance) than for the wild-type virus (Tamiflu-susceptible virus; WT) as an antibody. First, OHT-modified gold nanoparticles (OHT-GNPs) are used in a simple colorimetric assay as nanoprobes for the Tamiflu-resistant virus. In the presence of Tamiflu-resistant virus, they show a colorimetric change from deep red to purple because of the OHT-GNP aggregation driven by strong interactions between OHT and neuraminidase (NA) on the surface of the Tamiflu-resistance. Moreover, the color gradually turns purple as the concentration of the Tamiflu-resistant virus increases, allowing the determination of the presence of the virus with the naked eye. Furthermore, an OHT-based lateral flow assay (LFA) has been developed as a rapid and easy detection device for Tamiflu resistance. It shows detection specificity for various virus concentrations of Tamiflu-resistant virus even for the mixture of WT and Tamiflu-resistant viruses, where the limit of detection (LOD) is 5 × 102 ~ 103 PFU per test (=1 × 104 PFU/mL). It has been confirmed that this platform can provide accurate information on whether a virus exhibits Tamiflu resistance, thus supporting the selection of appropriate treatments using point-of-care (POC) diagnostics.

Salmonella is one of the most common foodborne pathogens, and Salmonella outbreaks are mostly associated with the intake of contaminated food or drink. Therefore, the rapid and sensitive on-site detection of Salmonella is very important. We report a naked eye detection method for Salmonella typhimurium using scanometric antibody probe. The antibody-attached glass substrate was treated with Salmonella typhimurium and the scanometric antibody probe was applied. After Ag enhancement of the probe, Salmonella typhimurium could be detected with the naked eye. The scanometric antibody probe was prepared by simply mixing Au nanoparticles, gold binding peptide-protein G, and antibody against Salmonella typhimurium. This probe can act as a signal enhancer and thus allows for an extremely simple, rapid, and efficient analysis of Salmonella typhimurium by the naked eye. We detected Salmonella typhimurium at a low concentration of 103 CFU/ml and clearly distinguished this bacterium from other foodborne pathogens. Furthermore, we successfully detected Salmonella typhimurium in milk, suggesting that this method can be useful in real-life samples. Because the scanometric antibody probe can be expanded to various types of antibodies, this naked eye detection method could be employed for the detection of various types of pathogens.

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.

A sophisticated set of an Au nanowire (NW) stimulator-Au NW detector system is developed for electrical cell stimulation and electrochemical analysis of subsequent exocytosis with very high spatial resolution. Dopamine release from a rat pheochromocytoma cell is more stimulated by a more negative voltage pulse. This system could help to improve the therapeutic efficacy of electrotherapies by providing valuable information on their healing mechanism.

It is highly important to identify influenza viruses rapidly and accurately for the prevention of future pandemic outbreaks. We developed an easy and sensitive influenza virus detection method using surface-enhanced Raman scattering (SERS) antibody probes. The SERS antibody probes can be prepared easily by mixing Au nanoparticles, gold binding peptide-protein G, and antibodies without complicated chemical or biological reactions. They also retain the optimal conformation for the antibody's interaction with Influenza A/CA/07/2009 (pH1N1), allowing us to detect pH1N1 sensitively and selectively. This method provides a detection limit of 4.1 × 103 TCID per mL and is highly selective for pH1N1. We anticipate that this method can be useful in a wide range of immunoassays.

Accurate detection of neuropeptides in cerebrospinal fluid (CSF) plays an important role in both indepth studies and early diagnosis of neurological diseases. Here, we report a biosensor based on Capacitive Micromachined Ultrasonic Transducer (CMUT) which is capable of detecting low concentrations (pg $\sim $ ng/ml) of a neuropeptide involved with the progression of Alzheimer's diseases, somatostatin (SST). A 10-MHz CMUT was fabricated and utilized as a physical resonant sensor which detects the change in the concentration of analyte through the mass-loading mechanism. The resonant plate was sequentially coated with protein G and antibodies to provide specificity to SST; Cysteine-tagged protein G layer enables controlled immobilization of antibodies in a welloriented manner. The change in the resonant frequency of the CMUT sensor was measured after incubating the sensor in various concentrations of SST. The significant shifts in the resonant frequency were observed for SST concentrations in the range of 10 pg/ml $\sim 1$ ng/ml. Compared to the previously reported biosensors developed for SST detection, our sensor shows discernable responses for SST that are $\sim 6$ orders of magnitude lower in concentration. Thus, this work demonstrates the potential of the CMUT resonant sensor as a promising biosensor platform for detection of neuropeptides involved with neurodegenerative diseases that often exist in low concentrations in CSF.

Dopamine (DA), an organic chemical neurotransmitter in the human brain, plays important roles in neuronal reward, motor control, and decision making. Thus, accurate quantification of DA concentration is essential for the investigation of various dopaminergic neural circuits and diagnosis of neurological diseases. Herein, we report an overoxidized polypyrrole/sodium dodecyl sulfate (SDS)-modified multi-walled carbon nanotube (OPPy/SDS-CNT) electrode which allows detection of DA with high resolution and selectivity. By using SDS as a dopant and sodium hydroxide (NaOH) as an oxidizing agent, highly sensitive detection of DA down to 5 nM with a detection limit of 136 pM is achieved. Moreover, due to the strong electrostatic interaction between the negatively-charged electrode and the positively-charged DA molecules, selective electrochemical detection of DA is successfully demonstrated in the presence of ascorbic acid (AA) and glucose (Glc). Lastly, by demonstrating in vitro detection of DA secreted from dopaminergic cells (PC12 cells) and examining biocompatibility of the electrode, we show the potential of our OPPy/SDS-CNT electrode as a promising candidate for a functional neural interface for in vitro and in vivo monitoring of DA concentrations.

Bimetallic nanostructures can provide distinct and improved physicochemical properties by the coupling effect of the two metal components, making them promising materials for a variety of applications. Herein, we report composition-selective fabrication of ordered intermetallic Au-Cu nanowires (NWs) by two-step chemical vapor transport method and their application to nano-electrocatalytic glucose detection. Ordered intermetallic Au3Cu and AuCu3 NWs are topotaxially fabricated by supplying Cu-containing chemicals to pre-synthesized single-crystalline Au NW arrays. The composition of fabricated Au-Cu NWs can be selected by changing the concentration of Cu-containing species. Interestingly, Au3Cu NW electrodes show unique electrocatalytic activity for glucose oxidation, allowing us to detect glucose without interference from ascorbic acid. Such interference-free detection of glucose is attributed to the synergistic effect, induced by incorporation of Cu in Au. We anticipate that Au3Cu NWs could show possibility as efficient nano-size electrochemical glucose sensors and the present fabrication method can be employed to fabricate valuable ordered intermetallic nanostructures.

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 nanogap-rich 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 tumor-bearing 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.

We present calculations for Lys-(H(2)O)(n) (n = 2, 3) to examine the effects of microsolvating water on the relative stability of the zwitterionic vs canonical forms of Lys. We calculate the structures, energies, and Gibbs free energies of the conformers at the B3LYP/6-311++G(d,p), wB97XD/6-311++G(d,p), and MP2/aug-cc-pvdz levels of theory, finding that three water molecules are required to stabilize the Lys zwitterion. By calculating the barriers of the canonical ↔ zwitterionic pathways of Lys-(H(2)O)(3) conformers, we suggest that both forms of Lys-(H(2)O)(3) may be observed in low temperature gas phase.