Compact and low-cost biosensor based on novel approach to spectroscopy of surface plasmons

A high-performance surface plasmon resonance (SPR) sensor based on a novel approach to spectroscopy of surface plasmons is reported. This approach employs a special diffraction grating structure (referred to as surface plasmon resonance coupler and disperser, SPRCD) which simultaneously couples light into a surface plasmon and disperses the diffracted light for spectral readout of SPR signal. The developed SPRCD sensor consists of a miniature cartridge integrating the diffraction grating and microfluidics and a compact optical system which simultaneously acquires data from four independent sensing channels in the cartridge. It is demonstrated that the SPRCD sensor is able to measure bulk refractive index changes as small as 3 × 10⁻⁷ RIU (refractive index units) and to detect short oligonucleotides in concentrations down to 200 pM.     

A new surface plasmon resonance sensor for high-throughput screening applications

We report a new high-throughput surface plasmon resonance (SPR) sensor based on combination of SPR imaging with polarization contrast and a spatially patterned multilayer SPR structure. We demonstrate that this approach offers numerous advantageous features including high-contrast SPR images suitable for automated computer analysis, minimum crosstalk between neighboring sensing channels and inherent compensation for light level fluctuations. Applications of a laboratory prototype of the high-throughput SPR sensor with 108 sensing channels for refractometry and biosensing are described. In refractometric experiments, the noise-limited refractive index resolution of the system has been established to be 3 x 10(-6) refractive index unit (RIU). Experimental data on detection of human choriogonadotropin (hCG) suggest that in conjunction with monoclonal antibodies against hCG, the reported SPR imaging sensor is capable of detecting hCG at concentrations lower than 500 ng/ml.     

Combination of Digital Image Processing and Statistical Data Segmentation to Enhance SPR and SPRi Sensor Responses

The work reports the combination of basic digital image processing (DIP) techniques and statistical segmentation strategy (SDS) to improve surface plasmon resonance curve (SPRc) and SPR imaging (SPRi) sensors' performance. The SPR image is used for sensing and monitoring biological events in the so-called SPR imaging process. In the traditional SPR process based on the attenuated total reflection (ATR) method, the image is used to create the SPR curve, and the curve features tracking is employed on sensing applications. The SPR curve features are enhanced after the pixels of the SPR image have been processed with low-complexity filters in the spatial domain (brightness, contrast, threshold, and morphological). The bootstrap was used as a statistical processing approach, selecting lines and columns from the image that was less affected by imperfections and noises in the image detector, and consequently reducing the SPR sensor instrumentation disturbances. Experimental tests with reversible binding water-mixture were performed, and both image and statistical processing were reported. The combination of DIP and SDS approaches improves the extraction of the curve features, increasing the performance in terms of resonance position sensitivity to 81%.

     

Integrated optical surface plasmon resonance immunoprobe for simazine detection.

This paper presents the detailed design and characterisation of a regenerable integrated optical surface plasmon resonance immunoprobe as a detector for the triazine herbicide simazine. A sensor design theoretically optimised for use in the aqueous environment is presented and its fabrication described. Experimental results on the sensitivity to changes in bulk refractive index of the analyte and on non-specific binding of ovalbumin are presented. Binding inhibition immunoassays were conducted for simazine and the lower limit of detection determined to be 0.16 microgram/l using anti-simazine IgG antibodies and 0.11 microgram/l using anti-simazine Fab fragments. A sample test cycle of 20 min was established.     

High-Sensitivity Refractive Index Sensor Based on D-Shaped Photonic Crystal Fiber with Rectangular Lattice and Nanoscale Gold Film

We propose and investigate a D-shaped photonic fiber refractive index sensor with rectangular lattice based on surface plasmon resonance. In such sensor, the nanoscale gold metal film is deposited on the flat surface where it is side polished. Numerical results show that the average sensitivity of Au-metalized surface plasmon resonance (SPR) sensor could reach as high as 8,129 nm/refractive index unit (RIU) in the dynamic index range from 1.35 to 1.41 as well as 2,000 nm/RIU from 1.33 to 1.35. Compared to conventional Au-metalized SPR sensors, the performance of our device is obviously better, and the production process is greatly simplified.     

Double Plasmon-Induced Transparency in Hybrid Waveguide-Plasmon System and Its Application for Localized Plasmon Resonance Sensing with High Figure of Merit

We demonstrate multispectral sharp plasmon-induced transparency response in a hybrid waveguide-plasmon system. By using the classical mechanical model of coupled damped harmonic oscillators, a clear and intuitive interpretation of the construction of the double-electromagnetically induced transparency (EIT)-like phenomenon is provided. High figure of merit up to 28.8 of the system for localized plasmon resonance refractive index sensing is obtained. Narrow polarization-independent double EIT-like spectral response is constructed, which provides an efficient tool for possible applications on slow light, enhanced nonlinear effect, nanoplasmonic functional devices, and integrated optical circuit.     

On the Performance of Highly Sensitive and Accurate Graphene-on-Aluminum and Silicon-Based SPR Biosensor for Visible and Near Infrared

We demonstrate the numerical analysis of surface plasmon resonance biosensor based on graphene on aluminum and silicon. Employing matrix method, it is found that the proposed sensor exhibits high imaging sensitivity ～400 RIU^?1 to 550 RIU^?1 in a large dynamic range from visible to near IR region. It is observed that the application of monolayer or bilayer graphene over aluminum not only protects it from oxidation but also enhances the adsorption of biomolecules, which results in the detection of large refractive indices ranging from aqueous solution to biomolecules (refractive index 1.330 to 1.480) with overall high performance in terms of imaging sensitivity and detection accuracy.     

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.     

Short order nanohole arrays in metals for highly sensitive probing of local indices of refraction as the basis for a highly multiplexed biosensor technology

A small array of subwavelength apertures patterned in a gold film on glass was characterized for use as a biosensor. It is widely believed that such arrays allow the resonance of photons with surface plasmons in the metallic film. Surface plasmon methods (and other evanescent wave methods) are extremely well suited for the measure of real time biospecific interactions. An extremely high sensitivity of 88,000%/refractive index unit was measured on an array with theoretical active area of .09 microm2. The formation of a biological monolayer was monitored. Both sensitivity and resolution were determined through measurement. The measured resolution, for a sensor with an active area of less than 1.5 microm2, is 9.4 x 10(-8) refractive index units which leads to a calculated sensitivity of 3.45E6%/refractive index unit. These values far exceed theoretical and calculated values of other grating coupled surface plasmon resonance (SPR) detectors and prism based SPR detectors. Because the active sensing area can be quite small (.025 microm2) single molecule studies are possible as well as massive multiplexing on a single chip format.     

High-throughput SPR sensor for food safety

High-throughput surface plasmon resonance (SPR) biosensor for rapid and parallelized detection of nucleic acids identifying specific bacterial pathogens is reported. The biosensor consists of a high-performance SPR imaging sensor with polarization contrast and internal referencing (refractive index resolution 2 x 10(-7) RIU) and an array of DNA probes microspotted on the surface of the SPR sensor. It is demonstrated that short sequences of nucleic acids (20-23 bases) characteristic for bacterial pathogens such as Brucella abortus, Escherichia coli, and Staphylococcus aureus can be detected at 100 pM levels. Detection of specific DNA or RNA sequences can be performed in less than 15 min by the reported SPR sensor.     

Optical Fiber Micro-Taper with Circular Symmetric Gold Coating for Sensor Applications Based on Surface Plasmon Resonance

We describe a novel, fully symmetrical deposition method, based on a sputtering technique and use of a gold ring target for deposition of a gold layer uniform around the taper waist. With such a circular symmetric coating, the plasmon resonance effect in the fiber taper becomes completely independent of the polarization of the illuminating light. We have measured the complex refractive index of such sputtered gold layers. On this basis, model calculations have been performed to describe the plasmon resonance as a function of taper waist diameter, gold layer thickness, analyte interaction length, and analyte refractive index. Optimized parameters especially for measurement in aqueous solutions are derived from these theoretical calculations. Experimental results are shown to be in good agreement with the theoretical analysis.     

Ambiguous Refractive Index Sensitivity of Fano Resonance on an Array of Gold Nanoparticles

We investigate the optical response to refractive index changes of a Fano resonance occurring in a random array of gold nanoparticles supported on a glass substrate. The Fano resonance results from the interference between localized surface plasmon on a gold nanoparticle and the light reflected at the boundary of the glass substrate. We demonstrate that the sensitivity of the resonance to the refractive index of the surrounding medium is highly dependent on the excitation geometry and can assume either positive or negative values. We furthermore present a theoretical analysis explaining this behavior based on the rigorous coupled wave analysis (RCWA) as well as the island film theory.

     

Highly Sensitive Surface Plasmon Resonance Based D-Shaped Photonic Crystal Fiber Refractive Index Sensor

In this article, a D-shaped photonic crystal fiber based surface plasmon resonance sensor is proposed for refractive index sensing. Surface plasmon resonance effect between surface plasmon polariton modes and fiber core modes of the designed D-shaped photonic crystal fiber is used to measure the refractive index of the analyte. By using finite element method, the sensing properties of the proposed sensor are investigated, and a very high average sensitivity of 7700 nm/RIU with the resolution of 1.30 × 10^?5 RIU is obtained for the analyte of different refractive indices varies from 1.43 to 1.46. In the proposed sensor, the analyte and coating of gold are placed on the plane surface of the photonic crystal fiber, hence there is no necessity of the filling of voids, thus it is gentle to apply and easy to use.     

Portable 24-analyte surface plasmon resonance instruments for rapid, versatile biodetection

Field use of surface plasmon resonance (SPR) biosensors for environmental and defense applications such as detection and identification of biological warfare agents has been hampered by lack of rugged, portable, high-performance instrumentation. To meet this need, we have developed compact multi-analyte SPR instruments based on Texas Instruments' Spreeta sensing chips. The instruments weigh 3 kg and are built into clamshell enclosures measuring 28 cm x 22 cm x 13 cm. Functions are divided between an electronics unit in the base of the box and a fluidics assembly in the lid. Automated valves and pumps implement an injection loop flow system that allows sensors to be exposed to sample, rinsed, and treated with additional reagents (such as secondary antibodies) under computer control. Injected samples flow over the surfaces of eight sensor chips fastened into a temperature-controlled silicone flowcell. Each chip has 3 sensing regions, for a total detection of 24 areas that can be simultaneously monitored by SPR. Coating these areas with appropriate antibodies or other receptors allows a sample to be screened for up to 24 different substances simultaneously. The instruments report refractive index (RI) values every second, with a typical noise level of 1-3 x 10(-6) RI units. The design of the device is described, and performance is illustrated with detection of six distinct analytes ranging from small molecules to whole microbes during the course of a single experiment.     

Bragg-Scattered Surface Plasmon Microscopy: Theoretical Study

We present a new approach to surface plasmon microscopy with high refractive index sensitivity and spatial resolution that is not limited by the propagation length of surface plasmons. It is based on a nanostructured metallic sensor surface supporting Bragg-scattered surface plasmons. We show that these non-propagating surface plasmon modes are excellently suited for spatially resolved observations of refractive index variations on the sensor surface owing to their highly confined field profile perpendicular to as well as parallel to the metal interface. The presented theoretical study reveals that this approach enables reaching similar refractive index sensitivity as regular surface plasmon resonance (SPR) microscopy and offers the advantage of improved spatial resolution when observing dielectric features with lateral size <10???m for the wavelength around 800?nm and gold as the SPR-active metal. This paper demonstrates the potential of Bragg-scattered surface plasmon microscopy for high-throughput SPR biosensing with high-density microarrays.     

Developing portable widefield fundus camera for teleophthalmology: Technical challenges and potential solutions

A portable, low cost, widefield fundus camera is essential for developing affordable teleophthalmology. However, conventional trans-pupillary illumination used in traditional fundus cameras limits the field of view (FOV) in a snapshot image, and frequently requires pharmacologically pupillary dilation for reliable examination of eye conditions. This minireview summarizes recent developments in alternative illumination approaches for widefield fundus photography. Miniaturized indirect illumination has been used to enable compact design for developing low cost, portable, widefield fundus camera. Contact mode trans-pars-planar illumination has been validated for ultra-widefield fundus imaging of infant eyes. Contact-free trans-pars-planar illumination has been explored for widefield imaging of adult eyes. Trans-palpebral illumination has been also demonstrated in a smartphone-based widefield fundus imager to foster affordable teleophthalmology.     

Localized Surface Plasmon Resonance and Refractive Index Sensitivity of Metal–Dielectric–Metal Multilayered Nanostructures

The localized surface plasmon resonances of multilayered nanostructures are studied using finite difference time domain simulations and plasmon hybridization method. Concentric metal–dielectric–metal (MDM) structure with metal core and nanoshell separated by a thin dielectric layer exhibits a strong coupling between the core and nanoshell plasmon resonance modes. The coupled resonance mode wavelengths show dependence on the dielectric layer thickness and composition of core and outer layer metal. The aluminum-based MDM structures show lower plasmon wavelength compared with Ag- and Au-based MDM nanostructures. The calculated refractive index sensitivity (RIS) factor is in the order Ag–Air–Ag>Au–Air–Au>Al–Air–Al for monometallic multilayered nanostructures. Bimetallic multilayered nanostructures support strong and tunable plasmon resonance wavelengths as well as high RIS factor of 510 nm/refractive index unit (RIU) and 470 nm/RIU for Al–Air–Au and Ag-Air-Au, respectively. The MDM structures not only exhibit higher index sensitivity but also cover a wide ultraviolet–near-infrared wavelengths, making these structures very promising for index sensing, biomolecule sensing, and surface-enhanced Raman spectroscopy.     

Broadband Mid-Infrared Super-Resolution Imaging with Metallic Nanorod-Bridged Dimer Array

We propose a broadband mid-infrared super-resolution imaging system comprising a metallic nanorod-bridged dimer array. The imaging array enables super-resolution imaging of shaped dipole sources in the near field. A charge transfer plasmon (CTP) appears in a metallic nanorod-bridged dimer. By varying the radius of the junction, the plasmon resonance wavelength of CTP mode can be tuned into the mid-infrared region. Here, we investigate the broadband super-resolution imaging of the incoherent and coherent dipole sources at mid-infrared wavelengths. With the array pitch varying, we calculate the cross-sectional field intensity distributions at the source plane and the image plane by using the finite element method. The simulation results indicate that the broadband incoherent and coherent super-resolution imaging can be realized at mid-infrared wavelengths with the imaging array. The image quality is sensitively dependent on the source coherent, the array pitch, and the distance from the image plane to the array. In the same structural parameters, the image quality of coherent source of in-phase is lower than that of incoherent source. Increasing the array pitch improves the image quality but it also increases the size of the array. By reasonably choosing the array pitch of the array, the spatial resolution of ～λ/109 and ～λ/73 is obtained corresponding to the incoherent imaging case and coherent imaging case at the mid-infrared wavelength of 4390 nm. Moreover, the larger image-array distance results in the lower image quality.     

Multichannel,Line-Monitoring Sensing Approach Based on Long-Range Surface Plasmons

The refractive index resolution of a surface plasmon resonance (SPR) sensor has been significantly improved these years; however, higher sensing performance is always desired. In this work, we propose a line-monitoring, long-range SPR sensor whose resolution is much better than conventional SPR sensors. Also, in contrast to mono-channel detection, multichannel detection, using line-monitoring technique, can detect multiple channels concurrently. In this way, this system achieves a refractive index resolution of 4.0?×?10^??7 refractive index units and can monitor multiple molecular interactions simultaneously. Finally, a model experiment detecting the Escherichia coli bacteria has demonstrated the potential for biomedical applications of this system.     

Enhanced Sensitivity of Surface Plasmon Resonance Phase-Interrogation Biosensor by Using Silver Nanoparticles

It is demonstrated that the sensitivity of surface plasmon resonance phase-interrogation biosensor can be enhanced by using silver nanoparticles. Silver nanoparticles were fabricated on silver films by using thermal evaporation. Sizes of silver nanoparticles on silver thin film can be tuned by controlling the deposition parameters of thermal evaporation. By using surface plasmon resonance heterodyne interferometey to measure the phase difference between the p and s polarization of incident light, we have demonstrated that sensitivity of glucose detection down to the order of 10⁻⁸ refractive index units can be obtained.