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.     

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.     

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.     

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.     

Design Analysis of Refractive Index Sensor with High Quality Factor Using Au-Al<Subscript>2</Subscript>O<Subscript>3</Subscript> Grating on Aluminum

We propose a surface plasmon resonance (SPR)-based refractive index sensor using gold-alumina grating over aluminum film for biosensing. Conventional SPR sensor based on gold grating exhibits broader SPR dips whereas that based on aluminum grating exhibits narrow reflection dip. A narrow reflection dip is desirable as it provides good resolution and improves the accuracy of measurement. Aluminum is less stable and generally is not preferred for an SPR-based sensor. It is more prone to being oxidized, which reduces the sensitivity and increases the width of the reflection dip of the sensor. While gold cannot provide narrow SPR reflection dips, but is used as an SPR active metal due to its more chemical stability. In order to improve the accuracy of gold grating-based sensor while taking care of oxidation problem of aluminum, in this paper, we propose a gold grating over aluminum film for SPR-based sensor and show that this configuration improves the sensitivity and the detection accuracy of the conventional sensor. Moreover, the oxidation problem is reduced to some extent as a part of aluminum is covered with gold. In order to completely avoid the oxidation of aluminum, we further propose to cover the exposed part of the aluminum with alumina and show that this configuration further improves the accuracy by reducing the width of the SPR reflection dip without affecting the sensitivity significantly. Numerical simulations show that sensitivity of proposed sensor is 270.33°/RIU with quality factor of more than 267.65 RIU^?1.     

Comparison of Gold and Silver/Gold Bimetallic Surface for Highly Sensitive Near-infrared SPR Sensor at 1550 nm

A large majority of surface plasmon resonance (SPR) sensors reported in the literature are designed to operate in the visible electromagnetic spectrum. However, the near-infrared, particularly at the telecommunications wavelength of 1550 nm, is also especially attractive for SPR sensing applications. In fact, SPR sensors operating in this region benefit from narrower resonance and deeper field penetration. In this paper, we report a theoretical and experimental study of an SPR sensor operating at a fixed wavelength of 1550 nm. The influence of the choice of metals and the interrogation methods on the sensitivity of the resulting SPR sensor is investigated. Two types of sensor chips (simple gold (Au) and bimetallic silver/Au structure) and three interrogation methods (monitoring of the position of the reflectivity minimum, the position of the centroid, and the intensity evolution of the reflectivity) are examined. We show that a refractive index resolution of 2.7?×?10^?6 refractive index unit can be easily obtained, and with further optimization of the measurement system, the ultimate limit of detection is expected to be even lowered. Therefore, the approach discussed here already shows a promising potential for highly sensitive SPR sensors.     

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.     

Platinum Layers Sandwiched Between Black Phosphorous and Graphene for Enhanced SPR Sensor Performance

Highly sensitive surface plasmon resonance (SPR) sensor consisting of Ag-Pt bimetallic films sandwiched with 2D materials black phosphorus (BP) and graphene over Pt layer in Kretschmann configuration is analyzed theoretically using the transfer matrix method. Numerical results show that upon suitable optimization of thickness of Ag-Pt layers and the number of layers of BP and graphene, sensitivity as high as 412°/RIU (degree/refractive index unit) can be achieved for p-polarized light of wavelength 633 nm. This performance can be tuned and controlled by changing the number of layers of BP and graphene. Furthermore, the addition of graphene and heterostructures of black phosphorus not only improved the sensitivity of the sensor but also kept the FWHM of the resonance curve much smaller than the conventional sensor utilizing Au as plasmonic metal and hence improved the resolution to a significant extent. We expect that this new proposed design will be useful for medical diagnosis, biomolecular detection, and chemical examination.

     

Rational Selection of Nanorod Plasmons: Material, Size, and Shape Dependence Mechanism for Optical Sensors

The localized surface plasmon resonance dependence on surrounding medium refractive index of Ag, Al, Au, and Cu nanoparticles is examined by electrodynamic approach. The refractive index sensitivity and sensing figure of merit (FOM) dependence of selected metal nanoparticles with similar geometry shows that although, sensing relevant parameters are shape (i.e., aspect ratio), and material dependent below the width 20 nm, but above this size these parameters are material independent under similar geometrical conditions. We have concluded that at optimum size, however, Al shows much higher refractive index sensitivity (RIS) in comparison to Au, Cu, and Ag, but FOM is higher for Ag in comparison to other metals. The observed sensing behavior is expected due to parameters like surface scattering, dynamic depolarization, radiation damping, and interband transitions, which may influence the nanorod plasmons.     

Long Range Surface Plasmons for Observation of Biomolecular Binding Events at Metallic Surfaces

A long range surface plasmon (LRSP) is an electromagnetic wave propagating along a thin metal film with an order of magnitude lower damping than conventional surface plasmon (SP) waves. Thus, the excitation of LRSP is associated with a narrower resonance and it provides larger enhancement of intensity of the electromagnetic field. In surface plasmon resonance (SPR) biosensors, these features allow a more precise observation of the binding of biomolecules in the proximity to the metal surface by using the (label-free) measurement of refractive index (RI) variations and by SP-enhanced fluorescence spectroscopy. In this contribution, we investigate LRSPs excited on a layer structure consisting of a fluoropolymer buffer layer, a thin gold film, and an aqueous sample. By implementing such structure in an SPR sensor, we achieved a 2.4- and 4.4-fold improvement of the resolution in the label-free and fluorescence-based detection, respectively, of the binding of biomolecules in the close proximity to the surface. Moreover, we demonstrate that the sensor resolution can be improved by a factor of 14 and 12 for the label-free and fluorescence-based detection, respectively, if the biomolecular binding events occur within the whole evanescent field of LRSP.     

Highly Sensitive SPR Sensor Based on D-shaped Photonic Crystal Fiber Coated with Indium Tin Oxide at Near-Infrared Wavelength

A surface plasmon resonance (SPR) sensor based on D-shaped photonic crystal fiber (PCF) coated with indium tin oxide (ITO) film is proposed and numerically investigated. Thanks to the adjustable complex refractive index of ITO, the sensor can be operated in the near-infrared (NIR) region. The wavelength sensitivity, amplitude sensitivity, and phase sensitivity are investigated with different fiber structure parameters. Simulation results show that ～6000 nm/refractive index unit (RIU), ～148/RIU, and ～1.2?×?10⁶ deg/RIU/cm sensitivity can be achieved for wavelength interrogation, amplitude interrogation, and phase interrogation, respectively, when the environment refractive index varies between 1.30 and 1.31. It is noted that the wavelength sensitivity and phase sensitivity are more pronounced with larger refractive index. The proposed SPR sensor can be used in various applications, including medicine, environment, and large-scale targets detection.     

Metallic Grating-Assisted Fiber Optic SPR Sensor with Extreme Sensitivity in IR Region

We theoretically propose a surface plasmon resonance (SPR)-based fiber optic refractive index (RI) sensor. A surface plasmon exciting metallic grating formed with the alternation of indium tin oxide (ITO) and silver (Ag) stripes is considered on the core of the fiber. A thin film of silicon is used as an overlay. Silicon film not only protects the metallic grating from oxidation but also enhances the field to improve the device sensitivity. The sensor is characterized in terms of sensitivity, detection accuracy (DA), figure of merit (FoM), and quality factor (QF). The maximum sensitivity in the RI range 1.33 to 1.38 refractive index unit (RIU) is reported to be?~25 µm/RIU in infra-red region of investigation.

     

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.     

Doped Single-Wall Carbon Nanotubes in Propagating Surface Plasmon Resonance-Based Fiber Optic Refractive Index Sensing

We propose a surface plasmon resonance (SPR)-based fiber coupled refractive index sensing probe utilizing single-wall carbon nanotubes (SWCNTs) as the upper most layer. The sensor is designed by considering indium tin oxide (ITO) film on the bare core of a multi-moded step-index fiber, followed by the deposition of silicon, and then by that of the highly doped bundled SWCNTs layers. The film thicknesses of different constituent layers are optimized with respect to the sensitivity and the detection accuracy of the sensor. The theoretical analysis results in high sensitivity of 9.78 μm per refractive index unit (μm/RIU) for the optimized probe in the infra-red (IR) region of the electromagnetic (EM) spectrum.     

Giant Infrared Sensitivity of Surface Plasmon Resonance-Based Refractive Index Sensor

Surface plasmons (SPs), the coherent charge density oscillations of the electrons bound to the metal-dielectric interface, are dominating the research field of optics. One of the ubiquitous applications of SPs is in sensing. In the present work, we have theoretically studied a couple of surface plasmon resonance (SPR)-based fiber-coupled ultra-sensitive refractive index sensors working in the infrared (IR) region. Either of the copper (Cu) and aluminum (Al) is used as surface plasmon exciting layers in these sensing probes. On the top of the metal layer, field-enhancing graphene and silicon layers are considered. The probes are characterized in terms of sensitivity and detection accuracy (DA). The sensitivities of Cu- and Al-based optimized probes are obtained respectively to be 23.50 and 24 μm/refractive index unit (RIU). To ensure the probes’ compatibility with bio-samples, an extra bio-recognition layer of graphene has been considered over the silicon layer which resulted into the respective sensitivities of 20 and 19.50 μm/RIU for Cu- and Al-based probes with appreciably good DAs.     

Coupled plasmon-waveguide resonators: a new spectroscopic tool for probing proteolipid film structure and properties.

A variant of surface plasmon resonance (SPR) spectroscopy has been developed that involves a coupling of plasmon resonances in a thin metal film and waveguide modes in a dielectric overcoating. This new technique is referred to as coupled plasmon-waveguide resonance (CPWR) spectroscopy. It combines a greatly enhanced sensitivity (due to increased electromagnetic field intensities at the dielectric surface) and spectral resolution (due to decreased resonance linewidths), with the ability to directly measure anisotropies in refractive index and optical absorption coefficient in a dielectric film adsorbed onto the surface of the overcoating. Experimental data obtained with an egg phosphatidylcholine bilayer are presented to document these properties.     

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.     

A miniature fiber optic surface plasmon resonance sensor for fast detection of Staphylococcal enterotoxin B

A fiber optic surface plasmon resonance (SPR) biosensor for detection of Staphylococcal enterotoxin B (SEB) is reported. The sensor is based on spectral interrogation of surface plasmons in a miniature sensing element based on a side-polished single-mode optical fiber with a thin metal overlayer. For specific detection of SEB, the SPR sensor is functionalized with a covalently crosslinked double-layer of antibodies against SEB. The SPR biosensor is demonstrated to be able to detect ng/ml concentrations of SEB in less than 10 min.     

Sensitivity enhancement of spectral surface plasmon resonance biosensors for the analysis of protein arrays

A novel method for sensitivity enhancement of spectral surface plasmon resonance (SPR) biosensors was presented by reducing the refractive index of the sensing prism in the analysis of protein arrays. Sensitivity of spectral SPR biosensors with two different prisms (BK-7, fused silica) was analyzed by net shifts of resonance wavelength for specific interactions of GST–GTPase binding domain of p21-activated kinase-1 and anti-GST on a mixed thiol surface. Sensitivity was modulated by the refractive index of the sensing prism of the spectral SPR biosensors with the same incidence angle. The sensitivity of a spectral SPR biosensor with a fused silica prism was 1.6 times higher than that with a BK-7 prism at the same incidence angle of 46.2°. This result was interpreted by increment of the penetration depth correlated with evanescent field intensity at the metal/dielectric interface. Therefore, it is suggested that sensitivity enhancement is readily achieved by reducing the refractive index of the sensing prism of spectral SPR biosensors to be operated at long wavelength ranges for the analysis of protein arrays.     

Self-Referencing Plasmonic Array Sensors

A self-referencing plasmonic platform is proposed and analyzed. By introducing a thin gold layer below a periodic two-dimensional nano-grating, the structure supports multiple modes including localized surface plasmon resonance (LSPR), surface plasmon resonance (SPR), and Fabry-Perot resonances. These modes get coupled to each other creating multiple Fano resonances. A coupled mode between the LSPR and SPR responses is spatially separated from the sensor surface and is not sensitive to refractive index changes in the surrounding materials or surface attachments. This mode can be used for self-referencing the measurements. In contrast, the LSPR dominant mode shifts in wavelength when the refractive index of the surrounding medium is changed. The proposed structure is easy to fabricate using conventional lithography and electron beam deposition methods. A bulk sensitivity of 429 nm/RIU is achieved. The sensor also has the ability to detect nanometer thick surface attachments on the top of the grating.