Vol.2 No.2 2009

63/98

Research paper : Development of high-sensitivity molecular adsorption detection sensors (M. Fujimaki et al.)−143−Synthesiology - English edition Vol.2 No.2 (2009) Figure 1 shows the issues that must be solved in sensor development, performance that can be expected by solving the issues, and merit that can be gained through the performance gained. The sensor must detect the presence of a certain substance (sample) at high sensitivity, stably, and with low noise. For the development of this sensor, we applied the technology of detecting the change in dielectric environment resulting from specific adsorption of an analyte through the change in waveguide modeTerm 1 [1][2]. The characteristics of this technology and the scenario for achieving higher performance through this development are explained below.2.1 Principles of the EFC-WM sensor and expected performanceThe surface plasmonTerm 2 resonance (SPR) sensor is known as a biosensor that is available on the market mainly for R&D and has extremely similar mechanism to the evanescent-fieldTerm 3 -coupled waveguide-mode (EFC-WM) sensor that we developed[1]. To help understand the mechanism of the EFC-WM sensor, we shall briefly explain the measurement principle of the SPR sensor that is already available for practical application.In general, in the SPR sensor, a metal film is deposited onto the glass substrate surface with high refractive index, and a prism made from the same glass is placed on the opposite side of the metal film surface. Usually, Au and Ag are used for the metal film since surface plasmon resonance can be excited in them with visible light. Figure 2(a) shows the optical system frequently used in the SPR sensor. This optical configuration is called the Kretschmann configuration[3]. In the Kretschmann configuration, when the light is incoming from the prism under total reflection condition, the surface plasmon is excited on the metal film surface at a specific incidence angle. This angle of incidence is called the ‘resonance angle’. When the light is incoming at the resonance angle, the incident light combines with the surface plasmon and the intensity of reflected light decreases significantly. Since the surface plasmon is sensitive to the change of permittivity at the metal surface, this resonance angle changes when biomolecules are adsorbed on the surface and the intensity of reflected light changes greatly. The adsorption of biomolecules can be detected by detecting the change of the intensity of the reflected light. To detect only specific molecules, the metal surface is modified with a substance that specifically adsorbs the target molecule.The sensing plate used in the EFC-WM sensor has a reflective film and a transparent dielectric waveguide on the substrate glass[4][5]. Same optical system as the SPR sensor can be used for measurement. Figure 2(b) shows the optical configuration of the EFC-WM sensor using the Kretschmann configuration. When light is incoming via the prism as in the SPR sensor, coupling occurs with waveguide mode that propagates the waveguide and the incident light through the evanescent field generated at the reflected film at a certain angle of incidence (resonance angle). When light is incoming around this specific angle, the intensity of reflected light decreases significantly. Since the waveguide mode is sensitive to the surface condition as in the SPR mode, when biomolecules adsorb onto the waveguide surface, the aforementioned resonance angle changes and the intensity of reflected light changes. The EFC-WM sensor uses this intensity change of reflected light to detect the molecule adsorption.SPR sensor is a label-free detection method where the sample is not tagged with a labeling substance, and its greatest characteristic is having high sensitivity that enables sample detection without labeling. Therefore, the complex procedure of labeling is unnecessary, and detection can be carried out easily. Also, since the sample is not labeled, the properties and features of the original sample are not lost. Therefore, the behavior of the target molecule, for example, in what condition the specific molecules are adsorbed can be observed accurately. However, in terms of sensitivity, it is said to be double to triple-digit inferior to the highly sensitive detection method using labeling substance, such as the enzyme-linked immunosorbent assay (ELISA)[6] (however, direct comparison is difficult since sensitively is greatly influenced by various factors such as the type and size of the target molecule, capture method of the target molecule, measurement environment such as whether it is in blood or in buffer solution, or presence of foreign substance). The EFC-WM sensor is a label-free detection method as in the SPR sensor. Until now, the EFC-WM sensor fell behind the SPR sensor as a molecule adsorption sensor even with Fig. 1 Issues, expected performances, merits gained, and fields of application of the sensor.Fig. 2 (a) Optical configuration used in the SPR sensor. (b) Optical configuration used in the EFC-WM sensor.AntiterrorismEnvironmentalmeasurementHealthCheck-upDrug discoveryMedicineApplicationAccurate diagnosis; highly sensitive diagnosisAir conditioning not necessary; can be used outdoors(acid, alkali, corrosiveness, reactivity)Stable against sampleStable manufacturing; reduced manufacturing errorIncreased lifespan of sensorDoes not break when handlingPrevention of misdiagnosis by damageIdentification of disease in its early stageIdentification of various diseases, pathogens, bacteriaReduction of effects by foreign substance and nonspecific adsorptionStabilization of sensitivity against temperatureImproved chemical stabilityImproved physical stabilityDetection of small quantity or low concentration substanceDetection of small moleculesNoise reductionStabilityHigh sensitivityMerits gainedExpected performanceIssuesWG mode(a) SampleWaveguidelayerLight sourceDetectorPolarizingplatesPrismMetal filmLight sourceDetectorPrismSubstrateglass(b)Reflective filmSPRSampleθ PolarizingplatesSubstrate glass

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