-Pui Ho

Highly sensitive differential phase-sensitive surface plasmon resonance biosensor based on the Mach–Zehnder configuration

A high-sensitivity surface plasmon resonance (SPR) biosensor based on the Mach-Zehnder interferometer design is presented. The novel feature of the new design is the use of a Wollaston prism through which the phase quantities of the p and s polarizations are interrogated simultaneously. Since SPR affects only the p polarization, the signal due to the s polarization can be used as the reference. Consequently, the differential phase between the two polarizations allows us to eliminate all common-path phase noise while keeping the phase change caused by the SPR effect. Experimental results obtained from glycerin-water mixtures indicate that the sensitivity limit of our scheme is 5.5 x 10(-8) refractive-index units per 0.01 degrees phase change. To our knowledge, this is a significant improvement over previously obtained results when gold was used as the sensor surface. Such an improvement in the sensitivity limit should allow SPR biosensors to become a possible replacement for conventional biosensing techniques based on fluorescence. Monitoring of the bovine serum albumin (BSA) binding reaction with BSA antibodies is also demonstrated.

Graphene-gold metasurface architectures for ultrasensitive plasmonic biosensing

Graphene-gold metasurface architectures that can provide significant gains in plasmonic detection sensitivity for trace-amount target analytes are reported. Benefiting from extreme phase singularities of reflected light induced by strong plasmon-mediated energy confinements, the metasurface demonstrates a much-improved sensitivity to molecular bindings nearby and achieves an ultralow detection limit of 1 × 10(-18) m for 7.3 kDa 24-mer single-stranded DNA.

Structural, optical and magnetic properties of Co-doped ZnO nanorods with hidden secondary phases

Co-doped ZnO nanorods (composition: Zn(0.955)Co(0.045)O) were grown by a simple surfactant-assisted hydrothermal technique. The morphological, structural, optical and magnetic properties of the as-prepared nanorods were investigated by means of scanning electron microscopy, high-resolution transmission electron microscopy, x-ray diffraction, x-ray photoelectron spectroscopy, micro-Raman spectroscopy, micro-cathodoluminescence, and vibrating sample magnetometry (VSM). The results showed that the sample had rod-like morphology and that the preferential growth direction was along the c axis. While Co was successfully doped into the ZnO wurtzite lattice structure as revealed by several characterization techniques, hidden secondary phases of Zn(y)Co(3-y)O(4) (0≤y≤1) were also clearly detected by the micro-Raman spectroscopic technique. We propose that the predominant diffusion-limited Ostwald ripening crystal growth mechanism under the hydrothermal coarsening yielded such phase segregation. VSM results showed that the nanorods displayed relatively weak room-temperature ferromagnetism. We suggest that the origin of the ferromagnetism is probably due to the presence of the mixed cation valence of Co via a d-d double-exchange mechanism rather than the real doping effect. It is essential to control the crystal growth mechanism and defect states associated with the ferromagnetism in order to realize the intrinsic diluted magnetic semiconductors.

Detecting Phase Shifts in Surface Plasmon Resonance: A Review

Under certain conditions, a surface plasmon wave along a metal-dielectric interface can be excited by an optical beam. The reflected optical beam will then undergo changes in both intensity and phase. As the level of intensity or phase change is quite sensitive to the coupling conditions such as the molecule concentration on the metal surface, this phenomenon has been utilized for label-free detection of biological species and characterization of molecular interactions during the last two decades. Currently, most of the commercial surface plasmon resonance (SPR) sensors rely on the detection of absorption dip in angular or wavelength spectrum. However, recent researches have shown that phase detection has the potential to achieve lower limit of detection (LoD) and higher throughput. This paper, thus, intends to review various schemes and configurations for SPR phase detection. The performance advantages and disadvantages of various schemes will be emphasized. It is hoped that this paper will provide some insights to researchers interested in SPR sensing and help them to develop SPR sensors with better sensitivity and higher throughput.

Real-time protein biosensor arrays based on surface plasmon resonance differential phase imaging

This paper reports the application of differential phase surface plasmon resonance (SPR) imaging in two-dimensional (2D) protein biosensor arrays. Our phase imaging approach offers a distinct advantage over the conventional angular SPR technique in terms of utilization efficiency of optical sensor elements in the imaging device. In the angular approach, each biosensor site in the biosensor array requires a linear array of optical detector elements to locate the SPR angular dip. The maximum biosensor density that a two-dimensional imaging device can offer is a one-dimensional SPR biosensor array. On the other hand, the phase-sensitive SPR approach captures data in the time domain instead of the spatial domain. It is possible that each pixel in the captured interferogram represents one sensor site, thus offering high-density two-dimensional biosensor arrays. In addition, our differential phase approach improves detection resolution through removing common-mode disturbances. Experimental results demonstrate a system resolution of 8.8 x 10(-7)RIU (refractive index unit). Real-time monitoring of bovine serum albumin (BSA)/anti-BSA binding interactions at various concentration levels was achieved using a biosensor array. The detection limit was 0.77 microg/ml. The reported two-dimensional SPR biosensor array offers a real-time and non-labeling detection tool for high-throughput protein array analysis. It may find promising applications in protein therapeutics, drug screening and clinical diagnostics.

White-light spectral interferometry for surface plasmon resonance sensing applications.

A novel differential phase detecting surface plasmon resonance (SPR) sensor based on white-light spectral interferometry is presented. Our proposed scheme employs a white-light source for SPR excitation and measures the corresponding SPR phase change at the optimized coupling wavelength with fixed angle of incidence across the visible spectrum. Compared to existing laser based phase detecting schemes, this system offers optimal sensitivity and extended dynamic range of measurement without any compromise in phase detection resolution. Results obtained from sodium chloride solutions indicate that the detection limit is 
2.6×10⁻⁷ RIU over a refractive index range of 10⁻² RIU, which is considerably wider than that achievable by existing laser based approach, thus making our scheme very attractive for practical SPR sensing applications.

Surface-enhanced Raman scattering biosensor for DNA detection on nanoparticle island substrates

We present a study on the surface-enhanced Raman scattering (SERS) properties of Ag nanoparticle island substrates (NIS) and their applications for target oligonucleotide (OND) detection. It has been found that the surface nanostructure of NIS samples can be controlled with a good degree of reproducibility, and a high SERS enhancement can be achieved when the peak extinction wavelength of NIS is tuned to a spectral window (approximately 60 nm) between the excitation wavelength and the scattered Raman wavelength. The highest SERS enhancement was obtained from the NIS substrates with a nominal thickness of 50 A. Detection of target OND was performed with a sandwich format in which the target OND was hybridized both to a capture OND immobilized on the NIS substrate, and a detection OND conjugated with a Raman-active dye for SERS signal generation. We compare the detection performance of two strategies based on the use of the detection OND with or without the gold nanoparticle (Au-NP). Our results confirm that, when the detection OND is coupled to the Au-NP, a better sensitivity for the target OND detection, in terms of a wider dynamic range and a lower detection limit (0.4 fM versus 1 nM without Au-NP), would be achieved.

Application of white light-emitting diode to surface plasmon resonance sensors

Abstract In this paper, we show that white light-emitting diode (white LED) is a viable light source for replacing the commonly-used halogen lamp in spectral surface plasmon resonance (SPR) sensors. We have constructed an experimental setup and results obtained from glycerin–water mixtures clearly demonstrate the systems capability in resolving the shift in the SPR dip caused by a change in the glycerin concentration. The use of white LED has the obvious benefits of direct modulation, low cost, long operation lifetime, robustness and small size. These are important pre-requisites for future commercialization of the SPR sensing technology.

Surface Plasmon Resonance Biosensor Incorporated in a Michelson Interferometer With Enhanced Sensitivity

A novel double-pass phase-sensitive surface plasmon resonance (SPR) biosensor based on a Michelson interferometer with differential phase interrogation is presented. The new setup provides an intrinsic resolution enhancement of up to two times in terms of achievable detection sensitivity due to an amplification effect in the SPR phase change when we place the SPR sensor head in the signal arm of the interferometer so that the interrogating optical beam traverses the sensor surface twice. Experimental results obtained from saltwater mixtures and antibody-antigen binding reactions confirmed the expected sensitivity enhancement as compared to the conventional SPR biosensor based on a Mach-Zehnder interferometer

An aptamer-based bio-barcode assay with isothermal recombinase polymerase amplification for cytochrome-c detection and anti-cancer drug screening

Based on a recently reported ultra-sensitive bio-barcode (BBC) assay, we have developed an aptamer-based bio-barcode (ABC) alternative to detect a cell death marker cytochrome-c (Cyto-c) and its subsequent application to screen anti-cancer drugs. Aptamer is a short single-stranded DNA selected from a synthetic DNA library by virtue of its high binding affinity and specificity to its target based on its unique 3D structure from the nucleotide sequence after folding. In the BBC assay, an antigen (Ag) in analytes is captured by a micro-magnetic particle (MMP) coated with capturing antibodies (Abs). Gold nanoparticles (NPs) with another recognition Ab against the same target and hundreds of identical DNA molecules of known sequence are subsequently added to allow the formation of sandwich structures ([MMP-Ab1]-Ag-[Ab2-NP-DNA]). After isolating the sandwiches by a magnetic field, the DNAs hybridized to their complementary DNAs covalently bound on the NPs are released from the sandwiches after heating. Acting as an Ag identification tag, these bio-barcode DNAs with known DNA sequence are then amplified by polymerase chain reaction (PCR) and detected by fluorescence. In our ABC assay, we employed a Cyto-c-specific aptamer to substitute both the recognition Ab and barcode DNAs on the NPs in the BBC assay; and a novel isothermal recombinase polymerase amplification for the time-consuming PCR. The detection limit of our ABC assay for the Cyto-c was found to be 10 ng/mL and this new assay can be completed within 3h. Several potential anti-cancer drugs have been tested in vitro for their efficacy to kill liver cancer with or without multi-drug resistance.