Integrated Terahertz Surface Plasmon Resonance on Polyvinylidene Fluoride Layer for the Profiling of Fluid Reflectance Spectra

We design terahertz (THz) surface-plasmon-resonance (SPR) sensors using a ferroelectric polyvinylidene fluoride (PVDF) thin layer for biological sensing. The reflectivity properties based on SPR are described using transfer matrix method (TMM) and numerically simulated using finite-difference time domain (FDTD) method. The sensing characteristics of the structure are systematically analyzed through the examination of the reflectivity spectrum. The results reveal that the pronounced SPR resonance peak has quasi-linear relationship with the refractive index variation of the material under investigation. Through analyzing and optimizing the structural parameters of the THz SPR sensor, we achieved the theoretical value of the refractive index detection sensitivity as high as 0.393 THz/unit change of refractive index (RIU) for a 20-μm-thick liquid sample with a 10-μm PVDF layer. This work shows great promise toward realizing a THz SPR sensor with high sensitivity for identifying the signatures of biological fluid sample.     

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.     

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.     

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.     

偏振干涉角度调制SPR传感技术研究及应用进展

针对一种新兴生物检测方法——表面等离子体波共振(SPR)技术,文中SPR传感系统采用偏振干涉和角度调制方案,使SPR传感灵敏度与光复反射系数的模和相位都相关,从而实现较大线形范围内的高灵敏测量。同时开展了该SPR传感系统在环保领域的应用研究,SPR共振信号可实时随甲烷含量线性改变,气体检测灵敏度达到1 070ppm,实验结果验证了这种SPR传感技术的检测性能并显示了其在环保监测领域的应用潜力。     

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.     

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.     

A Speckle-Free Angular Interrogation SPR Imaging Sensor Based on Galvanometer Scan and Laser Excitation

A speckle-free fast angular interrogation surface plasmon resonance imaging (SPRi) sensor based on a diode-pumped all-solid-state laser and galvanometer is reported in this work. A bidirectional scan using a galvanometer realizes the fast scanning of the incidence angle. The experimental results showed that the time needed for completing an SPR dip measurement was decreased to 0.5 s. And through cascading an immovable diffuser and two diffusers rotating in opposite directions, laser speckle was eliminated. The dynamic detection range and the sensitivity reached 4.6 × 10⁻² and 1.52 × 10⁻⁶ refractive index unit (RIU), respectively, in a 2D array sensor when the angle scanning range was set as 7.5°. More importantly, the results demonstrated that the angular interrogation SPR imaging sensor scheme had the capability to perform fast and high-throughput detection of biomolecular interactions at 2D sensor arrays.

     

Analysis of protein interactions on protein arrays by a wavelength interrogation-based surface plasmon resonance biosensor

We have investigated whether surface plasmon resonance (SPR) sensors based on the wavelength interrogation are able to analyze protein interactions on protein arrays. The spectral SPR sensor was self-constructed and its detection limit, expressed as the minimal refractive index variation, was calculated to be 6.6x10(-5) with the signal fluctuation of 1.0x10(-5). The protein array surface was modified by a mixed thiol monolayer to immobilize proteins. Protein arrays were analyzed by the line-scanning mode of the SPR sensor, which scanned every 100 microm along the central line of array spots and the scanned results were presented by color spectra from blue to red. Glutathione S-transferase (GST)-rac1 caused a concentration-dependent increase of SPR wavelength shift on protein arrays. The surface structure of the protein arrays was analyzed by atomic force microscopy. Specific interactions of antigens with antibodies were analyzed on the protein arrays by using three antibodies and eight proteins. These results suggest that the wavelength interrogation-based SPR sensor can be used as the biosensor for the high-throughput analysis of protein interactions on protein arrays.     

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.     

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.     

Improving the Sensitivity of Fiber Surface Plasmon Resonance Sensor by Filling Liquid in a Hollow Core Photonic Crystal Fiber

Inspired by the classic theory, we suggest that the performance of a D-shaped fiber optical surface plasmon resonance (SPR) sensor can be improved by manipulating the fiber core mode. To demonstrate this, we propose a novel fiber SPR sensor based on a hollow core photonic crystal fiber with liquid mixture filled in the core. The fiber sensor design involves a side-polished fiber with gold film deposited on the polished plane and liquid filling. Numerical simulation results suggest that by tuning the refractive index of the liquid mixture, the predicted sensitivity will be over 6,430 nm/refractive index unit for an aqueous environment, which is competitive for fiber chemical sensing. This optimization method may lead to an ultrahigh sensitivityfiber optical biosensor.     

Parallel-scan based microarray imager capable of simultaneous surface plasmon resonance and hyperspectral fluorescence imaging

With the development of the microarray technology, demands for array detection techniques become higher and higher. For many microarrays, several biomolecular interactions occur simultaneously and the interplay of various factors that affect these interactions remains poorly understood. Detecting such interactions with a single technique can often be a difficult and complicated process. In this work we propose a combined technique which enables simultaneous angle-interrogation surface plasmon resonance (SPR) sensing and hyperspectral fluorescence imaging. This tandem technique offers two-dimensional imaging of the whole array plane. The refractive index information obtained from SPR sensing and the physicochemical properties obtained from fluorescence imaging provide a comprehensive analysis of biological events on the array-chip. In addition, SPR and fluorescence detection techniques confirm each other in experimental results to exclude false-positive or false-negative cases. In terms of SPR sensing performance, the refractive index resolution is 3.86 × 10⁻⁶ refractive index units (RIU), and the detection limit is 10⁴ cfu/ml of Escherichia coli bacteria. The resolving power and detection sensitivity of fluorescence imaging are approximately 20 μm and 0.61 fluors/μm², respectively. Finally, two model experiments, detecting the DNA hybridization and biotin–avidin interactions respectively, demonstrate the biomedical application of this system.     

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 Novel Diamond Ring Fiber-Based Surface Plasmon Resonance Sensor

We propose a highly sensitive novel diamond ring fiber (DRF)-based surface plasmon resonance (SPR) sensor for refractive index sensing. Chemically active plasmonic material (gold) layer is coated inside the large cavity of DRF, and the analyte is infiltrated directly through the fiber instead of selective infiltration. The light guiding properties and sensing performances are numerically investigated using the finite element method (FEM). The proposed sensor shows a maximum wavelength and amplitude interrogation sensitivity of 6000 nm/RIU and 508 RIU^?1, respectively, over the refractive index range of 1.33–1.39. Additionally, it also shows a sensor resolution of 1.67 × 10^?5 and 1.97 × 10^?5 RIU by following the wavelength and amplitude interrogation methods, respectively. The proposed diamond ring fiber has been fabricated following the standard stack-and-draw method to show the feasibility of the proposed sensor. Due to fabrication feasibility and promising results, the proposed DRF SPR sensor can be an effective tool in biochemical and biological analyte detection.     

Detection of Staphylococcus aureus enterotoxin B at femtomolar levels with a miniature integrated two-channel surface plasmon resonance (SPR) sensor

Surface plasmon resonance (SPR) biosensors offer the capability for continuous real-time monitoring. The commercial instruments available have been large in size, expensive, and not amenable to field applications. We report here an SPR sensor system based on a prototype two-channel system similar to the single channel Spreeta devices. This system is an ideal candidate for field use. The two-channel design provides a reference channel to compensate for bulk refractive index (RI), non-specific binding and temperature variations. The SPR software includes a calibration function that normalizes the response from both channels, thus enabling accurate referencing. In addition, a temperature-controlled enclosure utilizing a thermo-electric module based on the Peltier effect provides the temperature stability necessary for accurate measurements of RI. The complete SPR sensor system can be powered by a 12V battery. Pre-functionalized, disposable, gold-coated thin glass slides provide easily renewable sensor elements for the system. Staphylococcus aureus enterotoxin B (SEB), a small protein toxin was directly detectable at sub-nanomolar levels and with amplification at femtomolar levels. A regeneration procedure for the sensor surface allowed for over 60 direct detection cycles in a 1-month period.     

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.     

SPR Label-Free Biosensor with Oxide-Metal-Oxide-Coated D-Typed Optical Fiber: a Theoretical Study

In this article, a surface plasmon resonance (SPR) biosensor based on D-typed optical fiber coated by Al₂O₃/Ag/Al₂O₃ film is investigated numerically. Resonance in near infrared with an optimized architecture is achieved. Refractive index sensitivity of 6558 nm/RIU (refractive index unit) and detection limit of 1.5 × 10⁻⁶ RIU, corresponding to 0.4357 nm/μM and detection limit of 23 nM in BSA (bovine serum albumin) concentration sensing, are obtained. The analysis of the performance of the sensor in gaseous sensing indicates that this proposed SPR sensor is much suitable for label-free biosensing in aqueous media.

     

A polycarbonate based surface plasmon resonance sensing cartridge for high sensitivity HBV loop-mediated isothermal amplification

In this study, we report a simple, low-cost surface plasmon resonance (SPR)-sensing cartridge based on a loop-mediated isothermal amplification (LAMP) method for the on-site detection of the hepatitis B virus (HBV). For LAMP detection, a SPR based LAMP sensing system (SPRLAMP) was constructed, including a novel SPRLAMP sensing cartridge integrating a polymethyl methacrylate (PMMA) micro-reactor with a polycarbonate (PC)-based prism coated with a 50 nm Au film. First, we found that the change of refractive index of the bulk solution was approximately 0.0011 refractive index (RI) units after LAMP reaction. The PC-based prism's linearity and thermal responses were compared to those of a traditional glass prism to show that a PC-based prism can be used for SPR measurement. Finally, the HBV template mixed in the 10 μl LAMP solution could be detected by SPRLAMP system in 17 min even at the detection-limited concentration of 2 fg/ml. We also analyzed the correlation coefficients between the initial concentrations of HBV DNA templates and the system response (ΔRU) at varying amplification times to establish an optimal amplification time endpoint of 25 min (R(2)=0.98). In conclusion, the LAMP reaction could be detected with the SPRLAMP sensing cartridge based on direct sensing of the bulk refractive index.     

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.