Surface Plasmon Resonance Platform Research Articles

Label-free detection of rare cell in human blood using gold nano slit surface plasmon resonance.

Label-free detection of rare cells in biological samples is an important and highly demanded task for clinical applications and various fields of research, such as detection of circulating tumor cells for cancer therapy and stem cells studies. Surface Plasmon Resonance (SPR) as a label-free method is a promising technology for detection of rare cells for diagnosis or research applications. Short detection depth of SPR (400 nm) provides a sensitive method with minimum interference of non-targets in the biological samples. In this work, we developed a novel microfluidic chip integrated with gold nanoslit SPR platform for highly efficient immunomagnetic capturing and detection of rare cells in human blood. Our method offers simple yet efficient detection of target cells with high purity. The approach for detection consists of two steps. Target cells are firs captured on functionalized magnetic nanoparticles (MNPs) with specific antibody I. The suspension containing the captured cells (MNPs-cells) is then introduced into a microfluidic chip integrated with a gold nanoslit film. MNPs-cells bind with the second specific antibody immobilized on the surface of the gold nanoslit and are therefore captured on the sensor active area. The cell binding on the gold nanoslit was monitored by the wavelength shift of the SPR spectrum generated by the gold nanoslits.

Review of plasmonic fiber optic biochemical sensors: improving the limit of detection.

This paper presents a brief overview of the technologies used to implement surface plasmon resonance (SPR) effects into fiber-optic sensors for chemical and biochemical applications and a survey of results reported over the last ten years. The performance indicators that are relevant for such systems, such as refractometric sensitivity, operating wavelength, and figure of merit (FOM), are discussed and listed in table form. A list of experimental results with reported limits of detection (LOD) for proteins, toxins, viruses, DNA, bacteria, glucose, and various chemicals is also provided for the same time period. Configurations discussed include fiber-optic analogues of the Kretschmann–Raether prism SPR platforms, made from geometry-modified multimode and single-mode optical fibers (unclad, side-polished, tapered, and U-shaped), long period fiber gratings (LPFG), tilted fiber Bragg gratings (TFBG), and specialty fibers (plastic or polymer, microstructured, and photonic crystal fibers). Configurations involving the excitation of surface plasmon polaritons (SPP) on continuous thin metal layers as well as those involving localized SPR (LSPR) phenomena in nanoparticle metal coatings of gold, silver, and other metals at visible and near-infrared wavelengths are described and compared quantitatively. Graphical Artist rendering of light from a tilted fiber Bragg grating probing the cladding surface where a thin gold film and biofunctional layer are used to detects analytes

A gold nanorod-based localized surface plasmon resonance platform for the detection of environmentally toxic metal ions.

Gold nanorods (Au NRs) are elongated nanoparticles with unique optical properties which depend on their shape anisometry. The Au NR-based longitudinal localized surface plasmon resonance (longitudinal LSPR) band is very sensitive to the surrounding local environment and upon the addition of target analytes, the interaction between the analytes and the surface of the Au NRs leads to a change in the longitudinal LSPR band. This makes it possible to devise Au NR probes with application potential to the detection of toxic metal ions with an improved limit of detection, response time, and selectivity for the fabrication of sensing devices. The effective surface modification of Au NRs helps in improving their selectivity and sensitivity toward the detection of toxic metal ions. In this review, we discuss different methods for the preparation of surface modified Au NRs for the detection of toxic metal ions based on the LSPR band of the Au NRs and the types of interactions between the surface of Au NRs and metal ions. We summarize the work that has been done on Au NR-based longitudinal LSPR detection of environmentally toxic metal ions, sensing mechanisms, and the current progress in various modified Au NR-based longitudinal LSPR sensors for toxic metal ions. Finally, we discuss the applications of Au NR-based longitudinal LSPR sensors to real sample analysis and some of the future challenges facing longitudinal LSPR-based sensors for the detection of toxic metal ions toward commercial devices.

Real-time ligation chain reaction for DNA quantification and identification on the FO-SPR.

Different assays have been developed in the past years to meet point-of-care diagnostic tests requirements for fast and sensitive quantification and identification of targets. In this paper, we developed the ligation chain reaction (LCR) assay on the Fiber Optic Surface Plasmon Resonance (FO-SPR) platform, which enabled simultaneous quantification and cycle-to-cycle identification of DNA during amplification. The newly developed assay incorporated FO-SPR DNA melting assay, previously developed by our group. This required establishment of several assay parameters, including buffer ionic strength and thermal ramping speed as these parameters both influence the ligation enzyme performance and the hybridization yield of the gold nanoparticles (Au NPs) on the FO-SPR sensor. Quantification and identification of DNA targets was achieved over a wide concentration range with a calibration curve spanning 7 orders of magnitude and LOD of 13.75 fM. Moreover, the FO-SPR LCR assay could discriminate single nucleotide polymorphism (SNPs) without any post reaction analysis, featuring thus all the essential requirements of POC tests.

Nanoporous anodic alumina platforms: engineered surface chemistry and structure for optical sensing applications.

Electrochemical anodization of pure aluminum enables the growth of highly ordered nanoporous anodic alumina (NAA) structures. This has made NAA one of the most popular nanomaterials with applications including molecular separation, catalysis, photonics, optoelectronics, sensing, drug delivery, and template synthesis. Over the past decades, the ability to engineer the structure and surface chemistry of NAA and its optical properties has led to the establishment of distinctive photonic structures that can be explored for developing low-cost, portable, rapid-response and highly sensitive sensing devices in combination with surface plasmon resonance (SPR) and reflective interference spectroscopy (RIfS) techniques. This review article highlights the recent advances on fabrication, surface modification and structural engineering of NAA and its application and performance as a platform for SPR- and RIfS-based sensing and biosensing devices.

Leukemic marker detection using a spectro-polarimetric surface plasmon resonance platform

In this paper, we present a proof of concept screening for monoclonal immunoglobulin as a leukemia tumor marker using a surface plasmon resonance (SPR) bio-sensing platform. This screening method is based on measurements of immunoglobulin levels in human serum and the determination of the relative concentrations of kappa and lambda light chains. The kappa/lambda ratio is used to determine the presence of monoclonal immunoglobulin. Tests have been performed using standard solutions of immunoglobulins and serum samples from patients with known leukemic diagnoses. This platform has a resolution of 5×10−7 refractive index unit (RIU) per channel, which is up to 10 times better than other SPR imaging systems for multi-sensing applications. The results obtained with this technique are in agreement with those acquired using conventional methods for immunoglobulin detection, indicating that our polarimetric SPR platform should be suitable for a cheap and efficient tool for early leukemia biomarker screening and monitoring applications.

Enhanced antibody recognition with a magneto-optic surface plasmon resonance (MO-SPR) sensor

A comparison between sensing performance of traditional SPR (Surface Plasmon Resonance) and magneto-optic SPR (MOSPR) transducing techniques is presented in this work. MOSPR comes from an evolution of traditional SPR platform aiming at modulating Surface Plasmon wave by the application of an external magnetic field in transverse configuration. Previous work demonstrated that, when the Plasmon resonance is excited in these structures, the external magnetic field induces a modification of the coupling of the incident light with the Surface Plasmon Polaritons (SPP). Besides, these structures can lead to an enhancement in the magneto-optical (MO) activity when the SPP is excited. This phenomenon is exploited in this work to demonstrate the possibility to use the enhanced MO signal as proper transducer signal for investigating biomolecular interactions in liquid phase. To this purpose, the transducer surface was functionalized by thiol chemistry and used for recording the binding between Bovine Serum Albumin molecules immobilized onto the surface and its complementary target. Higher sensing performance in terms of sensitivity and lower limit of detection of the MOSPR biosensor with respect to traditional SPR sensors is demonstrated.

Tamm-plasmon and surface-plasmon hybrid-mode based refractometry in photonic bandgap structures

The transverse magnetic (TM) polarized hybrid modes formed as a consequence of coupling between Tamm plasmon polariton (TM-TPP) mode and surface plasmon polariton (SPP) mode exhibit interesting dispersive features for realizing a highly sensitive and accurate surface plasmon resonance (SPR) sensor. We found that the TM-TPP modes, formed at the interface of distributed Bragg reflector and metal, are strongly dispersive as compared to SPP modes at optical frequencies. This causes an appreciably narrow interaction bandwidth between TM-TPP and SPP modes, which leads to highly accurate sensing. In addition, appropriate tailoring of dispersion characteristics of TM-TPP as well as SPP modes could ensure high sensitivity of a novel SPR platform. By suitably designing the Au/TiO₂/SiO₂-based geometry, we propose a TM-TPP/SPP hybrid-mode sensor and achieve a sensitivity ≥900 nm/RIU with high detection accuracy (≥30 μm⁻¹) for analyte refractive indices varying between 1.330 and 1.345 in 600-700 nm wavelength range. The possibility to achieve desired dispersive behavior in any spectral band makes the sensing configuration an extremely attractive candidate to design sensors depending on the availability of optical sources.

Ultrasensitive and Ultrawide Range Detection of a Cardiac Biomarker on a Surface Plasmon Resonance Platform

One of the main challenges in the development of new analytical platforms for ultrasensitive bioaffinity detection is jointly achieving a wide dynamic range in target analyte concentration, especially for approaches that rely on multistep processes as a part of the signal amplification mechanism. In this paper, a new surface-based sandwich assay is introduced for the direct detection of B-type natriuretic peptide (BNP), an important biomarker for cardiac failure, at concentrations ranging from 1 aM to 500 nM. This was achieved using nanoparticle-enhanced surface plasmon resonance (SPR) where a DNA aptamer is immobilized on a chemically modified gold surface in conjunction with the specific adsorption of antiBNP coated gold nanocubes in the presence of the biomarker target. A concentration detection range greater than eleven orders of magnitude was achieved through dynamic control of only the secondary nanoparticle probe concentration. Furthermore, detection at low attomolar concentrations was also achieved in undiluted human serum.

Yeast cell assay with a surface plasma resonance sensor at multiple penetration depths

We demonstrated a novel yeast cell assay using a multiple depth surface plasmon resonance platform, which has three detection depths. In the study we first identified the minimal and maximum number of cells required for detection and then used the platform to conduct a drug potency study. The study showed that the rank order of potency for 3 drugs could be clearly determined and was the same regardless of the penetration depth used for the measurement. The rank order made sense based on their respective mechanism of action. However the data quality of the inhibition curve was best when measured at the 1500nm depth. The dose dependent response was noticeable even after only 15min treatment, which is much earlier than those from traditional methods. By comparing the response units obtained at 3 different penetration depths in various yeast cell assays, we have confirmed that simultaneously monitoring from multiple penetration depths likely offers advantages to better detect robust signals from yeast cells, which proves difficult with other optical sensors with a short penetration depth of <300nm. The assay could be broadly applicable to other rigid and spherical cell types for biology studies and for antibiotic discovery.

Enhanced magneto-optical SPR platform for amine sensing based on Zn porphyrin dimers

Ethane-bridged Zn porphyrins dimers (ZnPP) have been deposited by Langmuir–Schäfer (LS) deposition technique onto proper transducer layers for surface plasmon resonance (SPR) and magneto-optical surface plasmon resonance (MO-SPR) characterization techniques performed in controlled atmosphere. This last tool has emerged as a novel and very performing sensing technique using as transducer layers a combination of noble and magnetic layers deposited onto glass substrates. A magnetic actuation allows recording a magneto optical SPR signal which ensures best gas sensing performances in terms of signal to noise ratio, sensitivity and limit of detection parameters. Primary and secondary amines in vapour phase have been used as sensing analytes and a possible explanation of the mechanism as well as of the dynamics of the interaction with the sensing Zn Porphyrin layers is provided.

‘Phytochip’: On-chip detection of phytopathogenic RNA viruses by a new surface plasmon resonance platform

The surface plasmon resonance (SPR) based ‘Phytochip’ was developed to distinguish virus-infected plants from non-infected plants. The system detects DNA–RNA hybridization to show the presence of phytopathogenic viruses such as the RNA virus barley stripe mosaic virus (BSMV) in wheat leaves. To achieve this BSMV and wheat specific oligonucleotides, and a negative control yeast oligonucleotide, were immobilized on a SPR gold surface chip. After optimization of the hybridization parameters with purified wheat samples, wheat infected with BSMV resulted in detectable signals with both the BSMV and the wheat probes. In contrast, a hybridization reaction was not be detected with the negative probe. The method is fast and sensitive with a detection time of 3000s (50min), a detection limit of 14.7pgμl−1 BSMV RNA and a measuring range of 14.7–84pgμl−1 BSMV RNA (1.323–7.56ng BSMV RNA per 90μl sample). These characteristics, combined with the high throughput design, make it suitable for application in plant breeding and virus control.

Spherical Nucleic Acid Enhanced FO-SPR DNA Melting for Detection of Mutations inLegionella pneumophila

A home-built fiber optic surface plasmon resonance platform (FO-SPR) was applied to directly screen PCR amplified DNA for mutations. The FO-SPR sensor was used for real-time monitoring of DNA duplex melting during high resolution temperature cycling. The signal of the DNA melting was enhanced by means of gold nanoparticle labels. This FO-SPR genetic assay allowed for detection of single-point mutations (SNP) in less than 20 min. The concept was demonstrated for the analysis of 9 different serogroups of the bacterium Legionella pneumophila, a common human pathogen responsible for atypical pneumonia. FO-SPR allowed us to detect genetic mutations inhibiting PCR, which could lead to amplification bias when molecular diagnostics are applied for L. pneumophila detection. All serogroups were found to display unique melting temperatures, indicating that mutations have accumulated in the target sequence. In a next step, clinical samples of L. pneumophila were analyzed using the FO-SPR sensor. This technology was proven to be reliable for the detection of mutations for those samples that previously displayed ambiguous qPCR quantification results. When these results were benchmarked, FO-SPR results were found to be consistent with Sanger sequencing but not with fluorescence based DNA melting. The presented results convincingly advocate the advantages of FO-SPR as a high resolution and fast genetic screening tool that can compete with the current standard techniques for SNP detection.

Effect of periodicity on the performance of surface plasmon resonance sensors based on subwavelength nanohole arrays

Surface plasmon resonance platforms, based on arrays of nanoholes on gold films, were used to detect the binding of organic and biological molecules. Optical sensors were assembled using nanohole arrays with different resonance energies, tuned by adjusting the distance between the holes. A direct relationship between plasmon energy and bulk sensitivity to refractive index changes was verified experimentally. The highest sensitivity (ca. 463nm/RIU) was obtained for the (1,0) SPP mode, excited on an array of nanoholes with 455nm periodicity. Real-time monitoring of the specific biotin–streptavidin binding was also used to demonstrate the influence of transmitted light intensity and FWHM on the sensor performance.

Development of a surface plasmon resonance and nanomechanical biosensing hybrid platform for multiparametric reading

We have developed a hybrid platform that combines two well-known biosensing technologies based on quite different transducer principles: surface plasmon resonance and nanomechanical sensing. The new system allows the simultaneous and real-time detection of two independent parameters, refractive index change (Δn), and surface stress change (Δσ) when a biomolecular interaction takes place. Both parameters have a direct relation with the mass coverage of the sensor surface. The core of the platform is a common fluid cell, where the solution arrives to both sensor areas at the same time and under the same conditions (temperature, velocity, diffusion, etc.).The main objective of this integration is to achieve a better understanding of the physical behaviour of the transducers during sensing, increasing the information obtained in real time in one single experiment. The potential of the hybrid platform is demonstrated by the detection of DNA hybridization.

Radiative-surface plasmon resonance for the detection of apolipoprotein E in medical diagnostics applications

Surface plasmon resonance (SPR)-based sensors enable the rapid, label-free and highly sensitive detection of a large range of biomolecules. We have previously shown that, using silver-coated optical fibers with a high surface roughness, re-scattering of light from the surface plasmons is possible, turning SPR into a radiative process. The efficacy of this platform has proven for the detection of large biomolecules such as viruses, proteins and enzymes. Here, we demonstrate that by bringing together this novel emission-based fiber SPR platform with an improved surface functionalization process aimed at properly orienting the antibodies, it is possible to rapidly and specifically detect the regulation of human apolipoprotein E (apoE), a low-molecular-weight protein (~39kDa) known to be involved in cardiovascular diseases, Alzheimer's disease and gastric cancer. The results obtained clearly show that this new sensing platform has the potential to serve as a tool for point-of-decision medical diagnostics. From the Clinical EditorIn this study, a novel emission-based surface plasmon resonance platform using silver-coated optical fibers is described. Properly orienting antibodies on the surface enables rapid and specific detection of human apolipoprotein E (apoE).

SPR based biosensor using surface relief grating in transmission mode

Surface plasmon resonance platforms based on laser inscribed azo polymer surface relief diffraction gratings were used to detect the binding of organic and biological molecules. Optical sensors were assembled to operate in transmission mode, resulting in a very simple setup. This new approach is observed to present a high sensitivity when compared to other systems, such as SPR-based biosensors using nanoholes. The corrugated surface provides a relatively large surface area and the improved sensitivity to binding events is related to resonant plasmon enhancement on the surface relief grating. It was found that varying the periodicity from 400 to 410 nm does not improve efficiency, however changing the groove depth from 30 to 65 nm, resulted in a two-fold increase in sensitivity. An interesting result is that sensors with higher energy surface plasmons present higher sensitivity when compared to lower energy ones. This result can drive further studies toward improved surface plasmon-based sensors.

Direct comparison of the performance of Bloch surface wave and surface plasmon polariton sensors

We report on the direct experimental comparison of the sensitivity and figure of merit of biosensors based either on surface plasmon polaritons on metal layers or on Bloch surface waves on one dimensional photonic crystals. The comparison was carried out by making use of a commercial surface plasmon resonance platform that was slightly adapted for these experiments. Although the experimental conditions are not optimized for Bloch surface waves, our experiments demonstrate that both types of biosensors show a similar figure of merit for biochips deposited on low cost molded plastic substrates. For glass substrates with better optical quality, the increased homogeneity of the photonic crystals results in the Bloch surface wave sensors outperforming the surface plasmon polariton sensors by a factor 1.7 in terms of figure of merit. Considerations on the illumination bandwidth indicate options to further increase such a factor.

Cancer Biomarker Detection in Serum Samples Using Surface Plasmon Resonance and Quartz Crystal Microbalance Sensors with Nanoparticle Signal Amplification

Early detection of cancer is vital for the successful treatment of the disease. Hence, a rapid and sensitive diagnosis is essential before the cancer is spread out to the other body organs. Here we describe the development of a point-of-care immunosensor for the detection of the cancer biomarker (total prostate-specific antigen, tPSA) using surface plasmon resonance (SPR) and quartz crystal microbalance (QCM) sensor platforms in human serum samples. K(D) of the antibody used toward PSA was calculated as 9.46 × 10(-10) M, indicating high affinity of the antibody used in developing the assay. By performing a sandwich assay using antibody-modified nanoparticles concentrations of 2.3 ng mL(-1) (Au, 20 nm) and 0.29 ng mL(-1) (8.5 pM) (Au, 40 nm) tPSA in 75% human serum were detected using the developed assay on an SPR sensor chip. The SPR sensor results were found to be comparable to that achieved using a QCM sensor platform, indicating that both systems can be applied for disease biomarkers screening. The clinical applicability of the developed immunoassay can therefore be successfully applied to patient's serum samples. This demonstrates the high potential of the developed sensor devices as platforms for clinical prostate cancer diagnosis and prognosis.

ELISA and SPR Studies of Ricin Binding to β-Galactoside Analogs

Early detection of ricin toxin, a biothreat agent, is of critical importance because it can be produced in large quantities rapidly. Ricin binds to β-galactoside analogs; therefore, these glycans can be used to capture and detect the toxin. Here, we have compared the binding affinities (Kds) of ricin with a panel of β-galactoside analogs using two different biophysical techniques, quantitative enzyme-linked immunosorbent assay (ELISA) and surface plasmon resonance (SPR). We found that β-galactosides bind to ricin better than N-acetyl β-galactosamines on all surfaces. Second, ricin prefers to bind to densely packed glycans over sparsely packed glycans. Third, when the structure and density of the glycans are kept constant and only the spacer is varied, we found that the binding affinities of glycans attached via a hydrocarbon spacer are better than glycans attached via a short oligoethylene glycol spacer, presumably because the alkyl spacer provides a better spatial arrangement. We also observed that the ELISA platform is more sensitive than the SPR platform. Taken together, in addition to the glycan structure, glycan density, presentation, and assay conditions are important factors that modulate the binding affinities. These comparative quantitative studies revealed similarities and subtle differences in the binding of the same glycans attached to different surfaces and must be taken into consideration when developing glycan-based biosensors for ricin or other glycan binding proteins.