Raman spectroscopy is a spectroscopic method which indirectly measures molecular vibration and can identify molecules by obtaining their unique vibrational fingerprints. Raman spectroscopy has the advantage of non-invasive and label-free detection, but it has the problem of low sensitivity due to the very weak intensity of Raman scattered light. In order to make Raman spectroscopy high sensitivity, surface enhanced Raman scattering (SERS) induced via metallic nanostructures has been widely studied. SERS is attracting attention in various fields of analysis such as bioanalysis, material analysis, environmental analysis, and food analysis because of its high sensitivity and selectivity. However, SERS spectra of adsorbed molecules with similar structures have very similar shapes, making it difficult to discriminate molecules from their spectra. Especially, it is even more difficult to determine the mixing ratio of mixtures of those molecules. Thus, we focused on the use of machine learning to determine the mixing ratio of similar structural molecules on gold nanostructure. In this study, we fabricated gold nanostructures by depositing gold on a cyclo-olefin polymer (COP) film with periodical nanostructure. Then, self-assembled monolayer (SAM) of mixed benzene thiol derivatives, as a model of surface adsorbed molecules, were prepared on the surface of gold nanostructure, and measured SERS spectra. We examined several machine learning models that can accurately determine mixing ratios from the obtained spectra. As a result, we succeeded in determining the mixing ratios of molecules with approximately 99% accuracy, with multilayer perceptron (MLP) model being the most accurate.
In this study, two-dimensional photonic crystal (PhC) was developed using functionalized polymers and nanoimprint lithography (NIL) for biosensing applications. In addition, using functionalized polymer-based PhC, detection of DNA hybridization or potassium ion were successfully applied by changing of PhC design and base material. For detection of DNA hybridization, PhC cavity was fabricated using polymer. By introducing of cavity into PhC, surrounding refractive index change due to the DNA hybridization could be detected high sensitively. Furthermore, for detection of potassium ion, PhC was fabricated using ionophore contained plasticized poly (vinyl chloride) (PVC). By using ionophore contained PVC-based PhC, potassium ion was specifically extracted into the PhC by ionophore. Then, potassium ion could be detected by the optical characteristics change that attributed by the physical and chemical property change of base material. From these result shows that the functionalized polymer-based PhC enables to apply for developing of high sensitive optical biosensor.
Surface enhanced raman scattering (SERS) is known for its high sensitivity toward detection down to single molecule level under optimal conditions using surface plasmon resonance (SPR). To excite the SPR for SERS application, nanostructured noble metal supports such as a nanoparticle have been widely used. However, for excitation of SPR for SERS application using noble metal nanoparticle has several disadvantages such as sophisticated fabrication procedure and low reproducibility of SPR excitation efficiency. To overcome these disadvantages, in this study, plasmonic crystal (PC)-SERS substrate which has a periodic noble metal nanostructure was successfully fabricated rapidly and cost-effectively based on nanoimprint lithography (NIL).
We have developed the point-of-care therapeutic drug monitoring kit based on Raman Spectroscopy of tear fluid. In this study, we were examined a soft substrate for an optimal lattice based on nanoimprint lithography using cyclo-olefin polymer to improve the sensitivity for measuring drug concentration in tear fluid. This is photonics crystal which is one of the nano-photonics based device was fabricated. Target is Sodium Phenobarbital which is an anticonvulsant agent. We show the effectiveness of Surface Enhanced Raman Spectroscopy of tear fluid with soft substrate for point-of-care therapeutic drug monitoring.
Nanostructure and molecular interface have currently received the great attractions for highly efficient, simultaneously
analysis of a number of important biomolecules from proteomics to genomics. Outstanding optical property of noble
metal nanostructures, localized surface plasmon resonance (LSPR), is a powerful phenomenon used in many chemical
and biological sensing experiments. This report described two types of gold-capped nanostructures: nanoparticle and
nanopore which reveal the strong excitation of LSPR spectra in the UV-visible region. The optical absorbance properties
of these nanostructures governing its sensitivity to local environment were studied. The flexibility in design of the goldcapped
nanostructures was evidently displayed on the wide-range capacity to develop in many types, from single to
multiple to microfluidic formats. Moreover, chemical modifications on the nanostructure surface were thoroughly
exploited to archive a highly sensitive protein and gene sensors such as using Protein A linker for orientation antibody or
using specific binding of streptavidin and biotinylated PNA or DNA probes... Lastly, we introduced a new form of
optical sensor, involving the coupling between interferometry and LSPR properties on the surface of gold-capped
nanopore structure. Our optical biosensing devices connecting with the gold-capped nanostructures including both
nanoparticle and nanopore are applicable to highly sensitive monitoring the interactions of other biomolecules, such as
proteins, whole cells, or receptors with a massively parallel detection capability in a highly miniaturized package.
Biosensors in connection with enzyme linked immunosorbent assay (ELISA) can be applied in many fields of research. In this paper, the reduction in the size of ELISA utilizing micro-chemical reaction is described in a microchamber array chip, and also a micro-flow antibody chip. The chips were fabricated by micro electromechanical system (MEMS) technology. The quantitative determination of dioxins was performed by using the chips. Glass or polystyrene beads were used for immobilization of an antibody at these chips. The antibody-immobilized beads were introduced into micro-flow channel or microchamber. As a competitive ELISA, sample solution mixed with horseradish peroxidase (HRP)-conjugated antigen, and non-HRP conjugated antigen was allowed to react in the microchamber or flow channel. As a sandwich assay, sample solution and HRP-conjugated antibody were sequentially added to the chamber. After the antigen-antibody reaction, addition of PBS buffer, hydrogen peroxide, and fluorogenic substrate produced the fluorescent dye. The resulting change in the fluorescence intensity was monitored by a fluorescence microscope.
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