Prism-coupled Surface Plasmon Resonance Research Articles

High spatial resolution surface plasmon resonance imaging using a plasmonic chip.

The surface plasmon resonance (SPR) technique has been widely applied to biosensing technologies for the rapid quantification of biomolecules without enzyme and fluorescent labeling. However, the conventional prism-coupling SPR method generally has a detection area of a few mm2, and the large contribution of the background signal forms a barrier to highly sensitive detection. Based on a highly spatially resolved SPR method, the present study constructed a scanning GC-SPR imaging instrument using an objective lens with a high numerical aperture and a plasmonic chip that could be used for grating-coupled SPR. Focusing light on the diffraction limit can suppress background signals and improve detection sensitivity. SPR imaging can also be performed by scanning a focal spot. Using this method, the refractive index of a mixture of water and dimethyl sulfoxide was measured with a detection accuracy of 2.43 × 10-3 RIU. Polydopamine films prepared with a thickness of <5nm were also measured, and each film thickness was evaluated with high sensitivity from the effective refractive index detected in a small area of <1 µm2.

An ultra-sensitive biosensor based on surface plasmon resonance and weak value amplification.

An ultra-sensitive phase plasmonic sensor combined with weak value amplification is proposed for the detection of IgG, as a model analyte. Phase detection is accomplished by self-interference between the p-polarization and the s-polarization of the light. With the principles of weak value amplification, a phase compensator is used to modulate the coupling strength and enhance the refractive index sensitivity of the system. On a simple Au-coated prism-coupled surface plasmon resonance (SPR) structure, the scheme, called WMSPR, achieves a refractive index sensitivity of 4.737 × 104 nm/RIU, which is about three times higher than that of the conventional phase-based approach. The proposed WMSPR biosensor gives great characteristics with a high resolution of 6.333 × 10-8 RIU and a low limit of detection (LOD) of 5.3ng/mL. The results yield a great scope to promote the optimization of other SPR biosensors for high sensitivity.

In Situ Analysis of Membrane-Protein Binding Kinetics and Cell-Surface Adhesion Using Plasmonic Scattering Microscopy.

Surface plasmon resonance microscopy (SPRM) is an excellent platform for in situ studying cell-substrate interactions. However, SPRM suffers from poor spatial resolution and small field of view. Herein, we demonstrate plasmonic scattering microscopy (PSM) by adding a dry objective on a popular prism-coupled surface plasmon resonance (SPR) system. PSM not only retains SPRM's high sensitivity and real-time analysis capability, but also provides ≈7 times higher spatial resolution and ≈70 times larger field of view than the typical SPRM, thus providing more details about membrane protein response to ligand binding on over 100 cells simultaneously. In addition, PSM allows quantifying the target movements in the axial direction with a high spatial resolution, thus allowing mapping adhesion spring constants for quantitatively describing the mechanical properties of the cell-substrate contacts. This work may offer a powerful and cost-effective strategy for upgrading current SPR products.

Label-free imaging and biomarker analysis of exosomes with plasmonic scattering microscopy.

Exosome analysis is a promising tool for clinical and biological research applications. However, detection and biomarker quantification of exosomes is technically challenging because they are small and highly heterogeneous. Here, we report an optical approach for imaging exosomes and quantifying their protein markers without labels using plasmonic scattering microscopy (PSM). PSM can provide improved spatial resolution and distortion-free image compared to conventional surface plasmon resonance (SPR) microscopy, with the signal-to-noise ratio similar to objective coupled surface plasmon resonance (SPR) microscopy, and millimeter-scale field of view as a prism-coupled SPR system, thus allowing exosome size distribution analysis with high throughput. In addition, PSM retains the high specificity and surface sensitivity of the SPR sensors and thus allows selection of exosomes from extracellular vesicles with antibody-modified sensor surfaces and in situ analyzing binding kinetics between antibody and the surface protein biomarkers on the captured exosomes. Finally, the PSM can be easily constructed on a popular prism-coupled SPR system with commercially available components. Thus, it may provide an economical and powerful tool for clinical exosome analysis and exploration of fundamental issues such as exosome biomarker binding properties.

(Invited) Measure Single Protein Size and Binding Kinetics with Plasmonic Scattering Imaging

Measuring individual protein properties is the most critical and challenging tasks for protein analysis. We show that it is possible to quantify single protein size and binding kinetics by plasmonic scattering imaging (PSM). The interference between the protein scattered light and the background light scattered by the rough substrate significantly enhances the signal intensity and contrast, which allows PSM to image single proteins, measure their sizes, and identify them based on their specific binding to antibodies. In addition, PSM can quantify protein binding kinetics by counting the binding of individual molecules, providing a digital method to measure binding kinetics and analyze heterogeneity of protein behavior. Furthermore, PSM can distinct specific and nonspecific binding processes by quantifying the mass and binding dynamics of individual bound analyte molecules, thus allowing the binding kinetic analysis in complex media such as serum. PSM can be implemented on top of an objective or a prism coupled surface plasmon resonance system, providing a convenient solution to realize high sensitivity single molecule imaging. We anticipate that PSM will become an important tool for single protein analysis, especially for low volume samples, such as single cells.

Quantification of Single-Molecule Protein Binding Kinetics in Complex Media with Prism-Coupled Plasmonic Scattering Imaging.

Measuring molecular binding is critical for understanding molecular-scale biological processes and screening drugs. Label-free detection technologies, such as surface plasmon resonance (SPR), have been developed for analyzing analytes in their natural forms. However, the specificity of these methods is solely relying on surface chemistry and has often nonspecific binding issues when working with samples in complex media. Herein, we show that single-molecule-based measurement can distinct specific and nonspecific binding processes by quantifying the mass and binding dynamics of individual-bound analyte molecules, thus allowing the binding kinetic analysis in complex media such as serum. In addition, this single-molecule imaging is realized in a commonly used Kretschmann prism-coupled SPR system, thus providing a convenient solution to realize high-resolution imaging on widely used prism-coupled SPR systems.

Dual-mode surface plasmon resonance sensor chip using a grating 3D-printed prism

The method for fabricating a grating prism surface plasmon resonance (SPR) sensor chip was developed. The grating prism was 3D-printed by a stereolithography 3D printer and subsequently created a grating pattern by soft lithography. A gold film was thermally evaporated on the grating prism. Moreover, a liquid cell was 3D-printed and assembled into a gold-coated grating prism. To make the sensor chip compact and practical, a compatible prism holder was 3D-printed by a fused deposition model 3D printer. The SPR sensor chip was mounted on the rotation stage and the SPR spectrum was recorded by spectrometer. The SPR excitation of the sensor chip can be extended to the near-infrared region by creating a grating pattern on the prism surface. A gold-coated grating prism exhibited dual modes of SPR excitations, namely, prism-coupling SPR (PC-SPR) and grating-coupling SPR (GC-SPR). The dual-mode SPR excitation was observed at the incident angles of 45°–80°. When the incident angle increased, the SPR excitation of the PC-SPR mode exhibited a blue shift in the wavelength region of 480–690 nm, whereas the GC-SPR mode exhibited a red shift in the wavelength region of 670–770 nm. The surface plasmon (SP) dispersion obtained from the dual-mode SPR configuration confirmed observable PC-SPR (which corresponded to + SP0 of the gold–resin interface) and GC-SPR (which corresponded to −SP+1 of the gold–air interface), which could be excited from the developed substrate. The refractive index sensitivities of the PC-SPR and GC-SPR modes were 2924.4 and 414.9 nm RIU−1, respectively. The SPR excitations of the sensor chip exhibited a simultaneous shift when the local refractive index of the materials adjacent to the gold-coated grating prism surface was changed, especially the material that had overlapping light absorption at the SPR excitation wavelength. Using this fabrication process, the prism is designed and then printed; moreover, the grating pattern on the prism surface can be employed to tune the SPR excitation wavelength of the sensor chip for the versatility and broad perspective of the optical sensing-based SPR.

Gaussian Beam Shaping and Multivariate Analysis in Plasmonic Sensing.

This work demonstrates a novel strategy to improve the sensing performance of a prism-coupled surface plasmon resonance system by Gaussian beam shaping and multivariate data analysis. The propagation of the beam along the optical system has been studied using the Gaussian beam approximation to design the incident beam such that the beam waist is aligned precisely and that stability is assured at the metal-dielectric interface. This renders a collimated incident beam, hence least angular dispersion, yielding a stronger and sharper plasmonic resonance. Moreover, we use the multivariate analysis method partial least squares that combines multiple features of the surface plasmon resonance curve and allows for a more precise analysis of the plasmonic response. Compared to univariate analysis, partial least squares improves typical sensing performance parameters remarkably. The combination of both aspects, beam shaping and multivariate analysis, overcomes current limitations of plasmonic detection systems. Thereby, we improve analytical sensitivity by a factor of 16, decrease the prediction error of the concentration of an unknown analyte by a factor of 11, and enhance resolution to the order of 5 × 10-7 RIU in angular interrogation.

Optimized sample addressing in prism-coupled surface plasmon resonance experiments

In this work we study the walk-off of the beam from the interrogation spot during rotation in surface plasmon resonance experiments using prism-based coupling such as the widespread Kretschmann configuration. The impossibility of maintaining a stationary footprint on the sensing surface with a fixed rotation axis can be of high importance. This would be specially so if samples are not homogeneous such as in arrays for multiplexing. By theoretically analyzing the behavior of the walk-off during rotation around an arbitrary fixed axis, we find an optimal and simple configuration to minimize this effect. The proposed setup is experimentally tested to verify the results and to show its ease of implementation. Interestingly, the conclusions reached may also be applied to other techniques employing reflection prisms.

Performance analysis of graphene-based surface plasmon resonance biosensor for blood glucose and gas detection

The present study exhibits excellent sensing characteristics of graphene-based prism-coupled surface plasmon resonance (SPR) biosensor for effectual sensing of both glucose concentrations in human blood samples in the range 25–175 mg/dl and gas with refractive index variations from 1.0000 to 1.0007 at a wavelength of 589 nm. The foremost attractiveness of the proposed SPR biosensor lies with excellent optical properties of N-FK51A-based glass prism along with the inclusion of a gold layer and a thin graphene layer. Transfer matrix method and angular interrogation technique are employed to envisage sharp SPR reflectance curves by optimizing the thickness of the gold layer and number of graphene layers. Aside this, an excellent electric field enhancement factor is accomplished near the graphene and sensing layer interface, which dramatically escalates the absorption of glucose and gas analytes. Subsequently, several performance measuring factors such as sensitivity, detection accuracy, resonance angle shift, and quality factor are thoroughly scrutinized and compared with other conventional SPR sensors. Moreover, simulation results reveal some noteworthy upshots like sensitivity of 275.15°/RIU, detection accuracy of 1.41/°, and quality factor of 76.2 that are obtained for glucose analytes, whereas sensitivity of 92.1°/RIU, detection accuracy of 2.55/° and quality factor of 230.2 are attained for gaseous analytes. Interestingly, it is found that the aforementioned parameters fitted excellently with a linear trend line, which leads to accurate investigation of glucose concentration as well as gaseous analytes. Hence the suggested structure opens up an avenue for suitable biomedical application.

Experimental demonstration of high sensitivity for silver rectangular grating-coupled surface plasmon resonance (SPR) sensing

We experimentally demonstrated a high sensitivity of surface plasmon resonance (SPR) sensor with silver rectangular grating coupling. The reflection spectra of the silver gratings indicated that surface plasmon resonance can be excited by either positive or negative order diffraction of the grating, depending on the period of the gratings. Comparing to prism-coupled SPR sensor, the sensitivities are higher for negative order diffraction coupling in bigger coupling angle, but much smaller for positive order diffraction coupling of the gratings. High sensitivity of 254.13 degree/RIU is experimentally realized by grating-based SPR sensor in the negative diffraction excitation mode. Our work paves the way for compact and sensitive SPR sensor in the applications of biochemical and gas sensing.

Common-path digital holographic microscopy for near-field phase imaging based on surface plasmon resonance.

We develop a common-path digital holographic microscopy based on prism-coupling surface plasmon resonance (SPR) for near-field phase imaging. A single beam splitter with specific configuration is introduced in an SPR imaging system to realize off-axis holographic recording. By measuring the phase shift difference of the reflected light at SPR exploiting the proposed holographic microscopy with high temporal stability, near-field characteristic measurement can be realized. With its simplicity, vibration isolation, and inherent capability of phase curvature compensation, the recommended system shows advanced performance in monitoring tiny refractive index variations and imaging biological tissues.

Optical integrated chips with micro and nanostructures for refractive index and SERS-based optical label-free sensing

Abstract: Label-free optical biosensing technologies have superior abilities of quantitative analysis, unmodified targets, and ultrasmall sample volume, compared to conventional fluorescence-label-based sensing techniques, in detecting various biomolecules. In this review article, we introduce our recent results in the field of evanescent-wavebased refractive index sensing and surface enhanced Raman scattering (SERS)-based sensing, both of which are promising platforms for label-free optical biosensors. First, silicon-on-insulator (SOI) nanowire waveguide and metallic surface plasmon resonance (SPR)-based refractive index sensing are discussed. In order to improve the detection limit, phase interrogation techniques are introduced to these types of sensors based on prism-coupled SPR and SOI microring resonators. A detection limit in the order of 10−6 refractive index unit is achieved. Detection of 16.7 pM anti-IgG is also demonstrated based on the SPR devices. Second, SERS substrates based on various nanometallic structures are discussed. Metallic nanowire arrays and inverted nanopyramids and grooves with a thin metal surface are fabricated based on anisotropic wetetching of silicon substrates. Both structures have demonstrated a Raman signal enhancement on the order of 107. In order to improve the extraction efficiency of the Raman signal at a high wave number, a nano-bowtie array substrate is fabricated, which exhibits double resonances at both the excitation wavelength and the desired Raman scattering wavelength. Experimental results have shown that this double-resonance structure can further enhance the received Raman signal, as compared to conventional SERS substrates with only one resonance at the excitation wavelength.

Phase detection sensitivity enhancement of surface plasmon resonance sensor in a heterodyne interferometer system

We propose a method of rotating the analyzer in front of the photodetector in a heterodyne interferometer system to implement optical phase shift and detection sensitivity enhancement of surface plasmon resonance (SPR) sensors. When the analyzer is rotated to shift the phase curve to be near the phase jump point, the phase detection sensitivity of the SPR sensor can be greatly enhanced. Theoretical calculations of a prism-coupled SPR device were performed using this method. Experimental result using an electro-optic heterodyne interferometer is reported.

Phase detection properties of grating-coupled surface plasmon resonance sensors

In this paper, the phase detection properties of a grating-coupled surface plasmon resonance (GCSPR) sensor with a thin metal film on the grating structure has been studied by performing finite-difference time-domain simulation first. Both the metal film thickness and modulation height of the grating considerably affect the phase detection properties of GCSPR sensors. The manner in which the metal film thickness affects the phase curve in the grating-coupled configuration is slightly different from that in the conventional prism-coupled surface plasmon resonance (PCSPR) configuration. For experiment, an electro-optic heterodyne interferometer is used to perform phase detection of the GCSPR sensor and a refractive index resolution of 1.5 × 0(-6) RIU are obtained. The results reveal that the phase detection sensitivity of the GCSPR sensor may be comparable to that of the PCSPR sensor.

Approach the angular sensitivity limit in surface plasmon resonance sensors with low index prism and large resonant angle

Surface plasmon resonance (SPR) sensors have been studied thoroughly for the past two decades. However, we found that the angular sensitivity in a prism-coupled SPR sensor can be as high as 500 deg/refractive index unit (RIU), which is two times higher than the sensitivity that has ever been achieved in previous studies. Such a high angular sensitivity can be fully achieved by simply choosing a proper low-index prism and a sufficiently large resonant angle for the light signal at an appropriate wavelength with an optimal metal film thickness. A feasible implementation of such an SPR sensor design concept was also proposed, and an even higher sensitivity of 600 deg/RIU can be achieved.

Long-range surface plasmons for sensitive detection of bacterial analytes

We report a novel prism-coupled surface plasmon resonance (SPR) biosensor based on special surface plasmon (SP) mode referred to as long-range surface plasmon (LRSP). Utilization of LRSP in prism-coupled SPR sensor offers several advantages in comparison with SPR sensors with conventional SPs (cSP) such as extended probe depth of LRSP mode into sensed dielectric and higher sensitivity to the bulk refractive index (RI) changes. The LRSP-supporting multilayer structures and prototype of the sensor setup were prepared. Performance of the LRSP-based sensor was compared to that of the cSP-based sensor in model experiments. LRSP-based sensor was determined to be almost 8 times more sensitive to sample RI changes than the cSP-based sensor. In addition, LRSP-based sensor responses were up to 2.5 and 5.5-fold greater than cSP-based sensor responses for latex beads and the bacterium E. coli HB101P, respectively.

Imaging of flow pattern in micro flow channel using surface plasmon resonance

We describe the visualization of the mixing and control of flow patterns in micro fluidic devices using a surface plasmon resonance (SPR) imaging sensor. We employed Kretschmann-type prism coupling SPR optics and an expanded laser diode light source via a single mode optical fibre. The reflected light was focused on a CCD camera. Two types of micro fluidic device were fabricated using photolithography and polymer imprinting a 2 mm wide, 100 µm high channel flow cell for the mixing and a slab channel device for flow control. We were able to observe mixing in the flow channel in real time with SPR imaging as the local refractive index change. Because the sensitivity of this system was limited within wavelength long distance from the gold surface, we could image the flow condition very near the channel wall. We also succeed in delivering the flow to a part of 4 × 4-array sensing area in a slab flow channel. These results will assist the development of integrated biosensors.

Surface plasmon resonance sensor based on the measurement of differential phase

A differential phase detection technique has been used for measuring the optical phase change associated with the surface plasmon resonance (SPR) effect that exists in a glass-metal-dielectric stack. A typical prism-coupled SPR setup was constructed and a Mach–Zehnder interferometer was used to perform interferometric analysis between the two orthogonal polarizations in the exit beam. By stepping the optical phase of the reference arm, one can measure the phase change caused by the SPR effect. Since the reference and signal beams traverse identical optical paths except for the section where phase detection is performed, we expect that this scheme can be more robust in terms of noise immunity. The interrogation area can be enlarged to enable imaging of the SPR sensing surface. Initial phase measurement obtained from a salt-water mixture is presented to demonstrate the operation of this technique. Our SPR sensing scheme provides a refractive index measurement sensitivity of 3.1×10−6 RIU which is comparable to the value reported for reflectivity-based SPR systems. The measured phase drift, which is a good indicator for the stability of the system, is within 6.6×10−3 rad/h. Within our experiments, the effect of the incident angle deviated from resonance on the sensitivity of SPR system has also been studied, thus demonstrating that the choice of incident angle is an important factor for achieving highest sensitivity.

Surface-plasmon-resonance investigations of Langmuir-Blodgett films of donor-acceptor substituted polyenes: linear optical and electro-optic properties

We present surface-plasmon-resonance (SPR) investigations on Langmuir-Blodgett films of two different types of donor-acceptor substituted polyenes. SPR spectroscopy in Kretschmann configuration enables determination of thickness and dielectric constants of films down to the monolayer range. The linear electro-optic susceptibilities χ (2)(− ω; ω,0) of mono- and multi-layer films are determined as dielectric constant changes Δε, which are seen as field-induced modulations in the mode-coupling condition in prism-coupled SPR. Knowing the magnitude and sign of χ (2)(− ω; ω,0) and the orientation angle of the molecules in the film, obtained from FT-IR spectroscopy, we were able to determine the second hyperpolarisability β(−ω;ω,0). In films of 7- N, N-dioctylaminophenyl-7,8′-diapocarotene-8′al, β is found to have a very high value of 7.7 × 10 −47 cm 3/V 2. The dependence of β on the film deposition type is discussed.