Vol.2 No.2 2009

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Research paper : Development of high-sensitivity molecular adsorption detection sensors (M. Fujimaki et al.)−153−Synthesiology - English edition Vol.2 No.2 (2009) Figure 1 is a summary by functions, “high sensitivity,” “high stability,” and “low noise.” Specific issues, merits obtained by solving each issue, and final target of application are summarized. This figure was inserted at the beginning of chapter 2. Also, the research scenario was shown as a diagram in Fig. 4, and added to the end of section 2.2.2 Summary of elemental technologies Question (Naoto Kobayashi)I understood that the main focus of the development of this paper was to improve sensitivity of the “evanescent-field-coupled waveguide-mode (EFC-WM) sensor” that has been already developed by forming pores with high aspect ratio in the waveguide so the number of molecules adsorbed to the waveguide surface would be increased and by measuring the change in reflectance due to the change in the waveguide mode by the adsorption, to improve the stability by the development of the monolithic sensing plate, and to further improve the sensitivity by detecting optical absorption of samples.Even though an EFC-WM sensor has more advantages than a SPR sensor in that there is no limitation on reflective substance and that both s and p waves can be used, why wasn’t it put to practical use?Answer (Makoto Fujimaki)The principle of the EFC-WM sensor has been known for a long time. The greatest reason it fell behind the SPR sensor for measuring molecular adsorption is because the absolute value of changes in resonance angle caused by molecular adsorption is smaller compared to the SPR sensor. Also, it has the disadvantage of requiring complex maneuvers to form the waveguide layer. I added these points in the latter half of section 2.1.Question (Naoto Kobayashi)I understood that one of the major contributions of the authors is to improve the sensitivity by making nano-sized pores with high aspect ratio. In this paper, it is described that the sensitivity is improved because the nanopores with high aspect ratio greatly increases the surface area to which the sample substance can be adsorbed, and because the sample substance is distributed within the waveguide in which the electric field is strongly confined. However, theoretical discussion using calculation and simulation is lacking. I recommend you include some quantitative explanation including the data for dependence of sensitivity on the density of pores.Answer (Makoto Fujimaki)To theoretically check the improvement of sensitivity by the nanopore formation, we conducted simulation using the Fresnel equation, and compared the results against the experimental values. In this sensor, sensitivity is higher when the full width at half maximum (W) of the dip is small and amount of shift (S) of the peak position is large. Namely, the sensitivity is higher when the S/W value is large. In the case of an EFC-WM sensor using a monolithic plate with nanopores, the increase in the S/W value by the nanopore formation was very large, about 4 times in the simulation and 6 times in the experimental value. We added this point in section 3.3 as a result showing the improvement of sensitivity.Question (Naoto Kobayashi)In the Breakthrough chapter, you mentioned that you realized an ultra–sensitive sensor (about 1000 times) using the reflectance change by optical absorption. In this case, what effects are there by the change of dielectric environment such as the change in refractive index and the change of resonance angle? Or, is there very little effect on the angle change due to extremely small amounts of adsorption? Even if that is so, do you think there is sufficient effect of the nanopores? If so, please explain. Also in this case, is the Kretschmann configuration optimal?Answer (Makoto Fujimaki)Angle change does occur in this case, but the adsorption is very small and hardly any angle change occurs. I added this in chapter 4. Although we haven’t conducted experiments yet, nanopores do have effect, and sensitivity will increase with pores. I added this also to chapter 4. For configuration, regardless of having or not having nanopores, it does not have to be always a Kretschmann configuration. However, this configuration is easy to use because it can be built readily and the optical system is simple.3 Synthetical approach Question (Naoto Kobayashi)In this study, I think the build up of synthesiology is still insufficient. In the paper, the content, significance, and effects of the individual elemental technologies are well described. However, I recommend you describe in detail the uniqueness and originality of synthesis in which the technologies were combined to create an ultra-sensitive, stable sensor.Answer (Makoto Fujimaki)In our research to increase the performance of the sensor, we used a synthesis method called strategic selection. First, to increase the sensitivity of EFC-WM sensor, which is our core technology, we selected nanoprocessing of the waveguide layer based on the simulation. To solve the problems of physical stability and evenness of the processed surface of the sensor, we returned to material selection, and selected the reflective film material suitable for the sensor. We found that Si was suitable as a reflective film, and decided to use the SOQ substrate consisting of a single-crystalline Si layer on a silica glass substrate. By strategically combining several elemental technologies, we were able to obtain an integrated technology in the form of a high-performance sensor. We added this description in chapter 5, and provided detailed explanation of Fig. 17.4 Future developments Question (Naoto Kobayashi)I think this research produced great results in ultra-sensitivity and stability of molecule adsorption sensor, but I think there are still many issues to be considered before it can be put to practical use in the medical scene. I hope you add the prospect for realization and the issues that must be solved.Answer (Makoto Fujimaki)In chapter 6, I added the prospect for realization and issues, which are mainly the reduction of noise or removal of foreign substance, the reduction of non-specific adsorption, and more accurate identification of samples to be detected. I also added comments about the cost. If these issues are solved, we expect this technology will be realized.5 Measures against pandemic influenza Question (Naoto Kobayashi)Will this technology help in the early detection of the new pandemic influenza virus that is currently spreading globally?Answer (Makoto Fujimaki)One of the themes on which our group is currently focusing our efforts is “ultra-sensitive detection and quick identification of new pandemic influenza virus.” We have so far succeeded in detecting the virus fragment (called the HA). Using the high-sensitive molecule detecting technology that we developed, in the near future, we wish to develop a device that can be used to prevent the spread of influenza pandemic.

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