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In this study, a surface plasmon resonance (SPR) biosensor with sub-wavelength grating waveguide for the real-time analysis of biomolecular interactions is developed. The conventional SPR has diffractive grating structure to increase the wave vector for exciting the surface plasmons and then detects biomolecular interactions in high order diffraction light. Using this approach has some disadvantages such as the intensity of high order diffraction light is dimmer to be difficult to measure and the measured reflectivity spectrum is too broadened. The proposed SPR biosensor uses a normally incident white light with the help of subwavelength grating structure and provides a sharper reflectivity spectrum according to waveguide interference both to avoid disadvantages of the conventional SPR biosensor with a grating coupler. When the diffraction grating waveguide structure and the condition of SPR are destroyed by external factors such as slight refractive index changes of the buffer or molecule adsorption on the grating surface, the optical path and momentum of the light coupled through the gold grating into the waveguide are changed and a resonance wavelength shift is induced as a result. By detecting this resonance wavelength shift, the SPR biosensor provides the ability to identify the kinetics of the biomolecular interaction on an on-line basis without the need for the extrinsic labeling of the biomolecules. The proposed biosensing metrology system becomes more simply and convenient for real-time biomolecular interaction analysis.

This study develops a coupled waveguide-surface plasmon resonance (CWSPR) biosensor with a sub-wavelength grating structure for the real-time analysis of biomolecular interactions. In the proposed optical metrology system, normally incident white light is coupled into the waveguide layer through the sub-wavelength grating structure thereby enhancing the wave vector which excites the surface plasmons on the metal sensing surface. The proposed CWSPR biosensor not only retains the same sensing sensitivity as that of a conventional surface plasmon resonance device, but also yields a sharper dip in the reflectivity spectrum and therefore provides an improved measurement precision. Moreover, the metrology setup overcomes the limitations of the conventional Kretschmann attenuated total reflection approach and is less sensitive to slight variations in the angle of the incident light. The experimental results confirm that the current CWSPR biosensor provides a straightforward yet powerful technique for real-time biomolecular interaction analysis.

A coupled waveguide-surface plasmon resonance (CWSPR) biosensor constructed with sub-wavelength grating structure is developed and used to analyze biomolecular interaction in real time. The normal incident white light is coupled into the waveguide layer through the sub-wavelength grating, and hence it has an enhanced wave vector to excite the localized surface plasmons on the metal grating surface. The CWSPR biosensor with the surface plasmon resonance (SPR) mode and the waveguide mode not only retains the same sensing sensitivity as that of a conventional SPR device, but also yields sharper dips in the reflectivity spectrum and therefore provides an improved measurement precision. Moreover, without the limitation of a conventional attenuated total reflection coupler and with the help of normal incidence, the system is more flexible and feasible for protein microarray and imaging applications.

This study utilizes a surface plasmon resona nce (SPR) biosensing to in vestigate the influence of secondary structures on the DNA hybridization and a surface-enhanced Raman scattering (SERS) spectrum to yield an alytical data regarding the structure of the oligonucleotides. It is found that the SPR angular shifts associated with the three pairs of 60mer oligonucleotides with prominent secondary structures are lower than those observed for the two pairs of oligonucleotides with no obvious secondary structures. It is also determined that increasing the DNA hybridization temperature from 35 o C to 45 o C reduces secondary structure effects. On the hybridization with mixture target oligonucleotides, the SPR results demonstrate that secondary structures interfere significantly. Although the kinetics of biomolecular interaction analysis is performed by using SPR sensor, the structural information of the o ligonucleotides can not observed directly. The SERS spect rum provides the structural information of the oligonucleotides with silver colloidal nanoparticles adapted as a Raman active substrate. Also, the detection limit of the DNA Raman signal has been successfully improved to reach sub- micro molarity of DNA concentration. Keywords : Structural change, DNA secondary structural effect, surface plasmon resonance, nanoparticles, surface-enhanced Raman scattering.

In this study, we use the finite-difference time-domain (FDTD) method and an attenuated-total-reflection (ATR) fluorescent optical microscope to investigate into the enhancement of near electro-magnetic (EM) field via plasmonic effects. In order to enhance the near EM field on the sensing surface, a metallic particle layer is added under the Kretschmann configuration of the conventional surface plasmon resonance sensor based on the ATR method. The affiliation by the simulation and experimental results can help us to understand the mechanisms of surface plasmons and particle plasmons on the sensor surface, and the effects of the EM field enhancement are classified as the surface plasmon effect, particle plasmon effect, interparticle coupling effect, and gap mode effect. By analyzing and comparing the results based on the FDTD method and the ATR fluorescent microscope, we can understand more about the plasmonic effects in order to deign a novel ultra-high resolution plasmonic biosensor.

In this paper, the reflection resonance spectrum of a sub-wavelength diffraction grating-coupled waveguide is used to analyze biomolecular interactions in real time. When the diffraction grating waveguide structure is destroyed by external factors such as slight refractive index changes of the buffer or molecule adsorption on the grating surface, the optical path of the light coupled through the grating into the waveguide is changed and a resonance wavelength shift is induced as a result. By detecting this resonance wavelength shift, the optical waveguide biosensor provides the ability to identify the kinetics of the biomolecular interaction on an on-line basis without the need for the extrinsic labeling of the biomolecules. A theoretical analysis of the sub-wavelength optical waveguide biosensor is performed. A biosensor with a narrow reflection resonance spectrum, and hence an enhanced detection resolution, is then designed and fabricated. Currently, the detection limit of the optical waveguide sensor is found to be approximately 10 -5 refractive index units. The developed biosensor is successfully applied to study the kinetics of an antibody interaction with protein G adsorbed on the sensing surface.

The interaction between tiny-molecular-weight analytes and receptors can be detected directly using advanced plasmonic biosensors. This paper proposes a plasmonic biosensor with Au nanoclusters embedded in a dielectric film. The sensor uses the attenuated total reflection (ATR) method to excite both the surface plasmons (SPs) and the particle plasmons (PPs). The local electro-magnetic (EM) field is enhanced by controlling the size and volume fraction of the embedded Au nanoparticles. The developed biosensor demonstrates a 10-fold improvement in resolution compared to a conventional surface plasmon resonance (SPR) biosensor. Using the proposed ultra-sensitive plasmonic biosensor, a direct detection approach is adopted to analyze the interactions of tiny molecules (< 200 Da) without the need for high molecular weight competitors or explicit labeling. The plasmonic biosensor developed in this paper provides a rapid diagnostic capability and has considerable potential for use in pharmaceutical research.

Current surface plasmon resonance (SPR) modes based on the attenuated total reflection (ATR) method can broadly be categorized as: conventional SPR, long-range SPR (LRSPR), coupled plasmon-waveguide resonance (CPWR), and waveguide-coupled SPR (WCSPR). Although the features of optical biosensors are dependent upon their particular SPR mode, a common requirement for all biosensors utilized for biomolecular interaction analysis (BIA) is a high degree of sensitivity. The current paper presents a theoretical analysis and comparison of the sensitivity and resolution of these four types of SPR biosensors when employed in three of the most prevalent detection methods, namely angular interrogation, wavelength interrogation, and intensity measurement. This study develops a detailed understanding of the influences of various biosensor design parameters in order to enhance the sensitivity and detection limit capabilities of such devices.

The present study proposes the use of a novel optical biosensor with Au nanoclusters embedded in a dielectric film to achieve a 10-fold improvement in the resolution performance. The proposed optical biosensor based on the attenuated total reflection (ATR) method excites both the surface plasmons (SPs) and particle plasmons (PPs) to enhance the local electro-magnetic field by controlling the size and volume fraction of the embedded Au nanoparticles to increase the resolution of the device. A co-sputtering method utilizing a multi-target sputtering system is used to fabricate the present dielectric films (SiO2) with embedded Au nanoclusters. It is shown that the sensitivity of the developed SPR biosensor can be improved by adjusting the size and volume fraction of the embedded Au nanoclusters in order to control the surface plasmon effect. The present gas detection and DNA hybridization experimental results confirm that the proposed Au nanocluster-enhanced SPR biosensor provides the potential to achieve an ultrahigh-resolution detection performance of approximately 0.1 pg/mm 2 surface coverage of biomolecules.

A novel surface plasmon resonance (SPR) imaging system based on modified Mach-Zehnder phase-shifting interferometry (PSI) measures the spatial phase variation of a resonantly reflected light in biomolecular interaction. In this technique, the SPR DNA microarray can diagnose the target DNA without additional labeling in real-time biomolecular interaction analysis (BIA). Owing to the feasible and swift measurements, the SPR microarray with this SPR imaging system can be extensively applied to the nonspecific adsorption of protein, the membrane-protein interaction, receptor-ligand interaction, DNA hybridization. The detection limitation of the SPR PSI imaging system is improved to about 1 pg/mm2 surface coverage of biomaterial for each individual spot over that of the conventional SPR imaging system that observe the intensity variation of a resonantly reflected light. The SPR PSI imaging system and its SPR microarray can provide the capability to analyze DNA hybridization or protein interaction in real-time, with high resolution, and at high-throughout screening rates.

The biosensors based on surface plasmon resonance (SPR) are often used as tools for directly detecting the kinetic interaction of unlabelled biological molecules at surface in real time. With the measured SPR reflection spectrum, we can detect a shift in the location and quantity of the reflection spectrum minimum and the half width at half maximum due to the change in the thickness or the refractive index of a thin dielectric film layer. The interested parameters of analyte layer or monolayer, like the molecular size and concentration, can be determined either with analytical approaches or linear data analysis approaches. Depends on the number of parameters need to be resolved, we may need either multiple spectra (two color method) or only one sensing spectrum under the assumption that the other film parameter is given for multiple parameters case. Although it is possible to estimate multiple parameters from only one sensing spectrum by linear estimation techniques, it suffers from not only the shortcoming for larger variance in the estimates from those techniques than that of multiple spectra method but also the difficulty for choosing the appropriate initial value in the estimation process. In this paper, we propose a modified analytic approach to attain suitable initial parameters that close enough to the exact value. Furthermore, we incorporated multi-experiment method into linear estimation algorithms to determine the optimal estimated parameters with smaller variability of the estimated parameters. In that manner, it would be benefit to reject the colored noise accidentally results from experiment process. The experimental data with the multi-experiment linear data analysis demonstrates that it has ability to sense slightly index change in consequence of argon gas flow through the nitrogen.