Jenq-Nan Yih

Optical waveguide biosensors constructed with subwavelength gratings

The reflection resonance spectrum of a subwavelength diffraction-grating-coupled waveguide is used to analyze biomolecular interactions in real time. 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 extrinsic labeling of the biomolecules. A theoretical analysis of the subwavelength 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 approximately 10(-5) refractive-index units. The biosensor is successfully applied to study of the dynamic response of an antibody interaction with protein G adsorbed on the sensing surface.

Angular-interrogation attenuated total reflection metrology system for plasmonic sensors.

We develop an angular-interrogation attenuated total reflection (ATR) metrology system for three different plasmonic sensors, namely, a conventional surface plasmon resonance (SPR) device, a coupled-waveguide SPR device, and a nanoparticle-enhanced SPR device. The proposed metrology system is capable of measuring the reflectivity spectra of the transverse magnetic mode and the transverse electric mode simultaneously. Through the optimal control of the fabrication process and use of sophisticated system instrumentation, the experimental results confirm that the developed ATR system is capable of measuring the resonant angle with an angular accuracy of 10(-4) deg.

A compact surface plasmon resonance and surface-enhanced Raman scattering sensing device

This paper presents an optical device capable of the simultaneous measurement of the surface plasmon resonance (SPR) spectrum, which provides information regarding the change in the dielectric constant of the binding analytes, and the surface-enhanced Raman scattering (SERS) spectrum, which yields analytical data regarding the structural changes of the analytes. SPR sensing is an established technology in the field of direct real-time analysis of biomolecular interactions such as antibodies/antigens, DNA hybridization, receptors/ligands, etc. Meanwhile, SERS sensing techniques represent a powerful means of acquiring and diagnosing structural information relating to analyte binding. This study adopts the attenuated total reflection (ATR) method and an Au nanocluster-embedded dielectric sensing film in developing a biosensor which integrates the SPR and SERS sensing techniques. The results confirm the effectiveness of the proposed multi-functional device in developing a detailed understanding of the mechanisms of biomolecular recognition.

Enhanced readout signal of superresolution near-field structure disks by control of the size and distribution of metal nanoclusters.

We present a study in which we enhance the carrier-to-noise ratio of a superresolution near-field structure (super-RENS) disk to read below 100-nm marks by implementing a mask layer comprising a Au nanocluster-embedded dielectric film. Various Au nanocluster-embedded mask layers are fabricated by a radio-frequency cosputtering process, and the size and distribution of Au nanoclusters are controlled. To verify the enhancement of the various films for super-RENS disk applications, the sensitivity enhancement of plasmonic gas sensing is demonstrated.

Angular distribution of polarized photon-pairs in a scattering medium with a Zeeman laser scanning confocal microscope.

A novel confocal microscope designed for use with turbid media is proposed. We use a Zeeman laser as the light source. Based on the properties of two‐frequency polarized photon‐pairs and the common‐path feature of polarized photon‐pairs with heterodyne detection employed in the proposed confocal microscope, three gatings (spatial filtering gating, polarization gating and spatial coherence gating) are thus simultaneously incorporated in the microscope. Experimental results for the angular distribution of polarized photon‐pairs in a scattering medium indicate that polarization gating and spatial coherence gating preclude the detection of multiply scattered photons, whereas the pinhole selects the least scattered photon‐pairs. Thus, better performance for axial resolution than can be obtained with a conventional confocal microscope is demonstrated experimentally. In addition, the proposed microscope is able to either look deeper into a turbid medium or work with a denser medium; furthermore, the axial resolution is improved.

Studying protein structural changes based on surface plasmon resonance and surface-enhanced Raman scattering

The ability to recognize the conformational changes and structural variations of a protein when immobilized in a solid surface is of great importance in a variety of applications. Surface plasmon resonance (SPR) sensing is an appropriate technique for investigating interfacial phenomena, and enables the conformational changes of proteins to be monitored through the variation in the SPR angle shift. Meanwhile, the surface-enhanced Raman scattering (SERS) system can also assist in clarifying the changes in protein structure. The present study utilizes a 1 mM CrO3 phosphate buffer solution (PBS) to induce conformational changes of human serum albumin (HSA). Monitoring the corresponding SPR angle shifts and the SPR reflectivity spectrum enables the relationships between the conformational changes of the surface-immobilized protein and the thickness and dielectric constants of the protein layer to be estimated. The experimental SPR results indicate that the Cr6+ ions cause significant conformational change of the protein. It is established that the ions are not merely absorbed into the protein as a result of electrostatic forces, but that complex protein refolding events also take place. Furthermore, the data acquired from the SERS system yield valuable information regarding the changes which take place in the protein structure.

Plasmon-enhanced optical waveguide biosensors constructed with sub-wavelength gold grating

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.

An investigation into the influence of secondary structures for DNA hybridization using surface plasmon resonance and surface-enhanced Raman scattering

This study utilizes a surface plasmon resonance (SPR) biosensing to investigate the influence of secondary structures on the DNA hybridization and a surface-enhanced Raman scattering (SERS) spectrum to yield analytical 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 oC to 45 oC 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 oligonucleotides can not observed directly. The SERS spectrum 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.

Investigating the structural changes of β-amyloid peptide aggregation using attenuated-total-reflection surface-enhanced raman spectroscopy

This study utilizes a surface-enhanced Raman spectroscopy (SERS) based on the attenuated-total-reflection (ATR) method to investigate that the structural information of the biomolecular monolayer on sensing surface can be dynamically observed with a higher signal-to-noise ratio signal. The secondary structures of long oligonucleotides and their influence on the DNA hybridization on the sensing surface are investigated. The SERS spectrum provides the structural information of the oligonucleotides with the help of a silver colloidal nanoparticle monolayer by control of the size and distribution of the nanoparticles adapted as a Raman active substrate. It is found that the ring-breathing modes of adenine, thymine, guanine, and cytosine in Raman fingerprint associated with three 60mer oligonucleotides with prominent secondary structures are lower than those observed for the two oligonucleotides with no obvious secondary structures. It is also determined that increasing the DNA hybridization temperature from 35°C to 45°C reduces secondary structure effects. The ATR-SERS biosensing technique will be used to provide valuable structural information regarding the short-term reversible interactions and long-term polymerization events in the A&bgr; aggregates on the sensing surface.

A label-free optical waveguide biosensor with sub-wavelength gratings

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.