Unraveling the Dynamics of SARS-CoV-2 Mutations: Insights from Surface Plasmon Resonance Biosensor Kinetics.

Surface Plasmon Resonance (SPR) technology is known to be a powerful tool for studying biomolecular interactions because it offers real-time and label-free multiparameter analysis with high sensitivity. This article summarizes the results that have been obtained from the use of SPR technology in studying the dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutations. This paper will begin by introducing the working principle of SPR and the kinetic parameters of the sensorgram, which include the association rate constant (ka), dissociation rate constant (kd), equilibrium association constant (KA), and equilibrium dissociation constant (KD). At the end of the paper, we will summarize the kinetic data on the interaction between angiotensin-converting enzyme 2 (ACE2) and SARS-CoV-2 obtained from the results of SPR signal analysis. ACE2 is a material that mediates virus entry. Therefore, understanding the kinetic changes between ACE2 and SARS-CoV-2 caused by the mutation will provide beneficial information for drug discovery, vaccine development, and other therapeutic purposes.

Clinical Application of a Graphene Oxide-Based Surface Plasmon Resonance Biosensor to Measure First-Trimester Serum Pregnancy-Associated Plasma Protein-A/A2 Ratio to Predict Preeclampsia.

Background: Preeclampsia, a major cause of adverse pregnancy outcomes, involves metalloproteinases pregnancy-associated plasma protein (PAPP)-A and PAPP-A2 from placental trophoblasts. The graphene oxide (GO)-based surface plasmon resonance (SPR) biosensor has higher sensitivity, affinity, and selective ability than the traditional SPR biosensor. The aim of this study was to explore the feasibility of measuring first-trimester serum PAPP-A/PAPP-A2 ratio as a novel predictor of preeclampsia using the GO-SPR biosensor. Methods: This prospective case-control study of pregnant women was conducted at MacKay Memorial Hospital, Taipei, Taiwan between January 2018 and June 2020. The SPR angle shifts of first-trimester serum PAPP-A, PAPP-A2, and PAPP-A/PAPP-A2 ratio measured using the GO-SPR biosensor were compared between preeclampsia and control groups. Results: Serum samples from 185 pregnant women were collected, of whom 30 had preeclampsia (5 early-onset; 25 late-onset). The response time between the antibody-antigen association and dissociation only took about 200 seconds. The SPR angle shift of PAPP-A in the preeclampsia group was significantly smaller than that in the control group (median (interquartile range): 5.33 (4.55) versus 6.89 (4.10) millidegrees (mDeg), P = 0.008). Conversely, the SPR angle shift of PAPP-A2 in the preeclampsia group was significantly larger than that in the control group (5.70 (3.81) versus 3.63 (2.38) mDeg, P < 0.001). Receiver operating characteristic (ROC) curve analysis revealed a cut-off PAPP-A/PAPP-A2 ratio to predict all preeclampsia of ≤ 0.76, with an area under the ROC curve (AUC) of 0.79 (95% CI 0.73-0.85, P < 0.001). Sub-group analysis revealed a cut-off PAPP-A/PAPP-A2 ratio to predict early-onset preeclampsia of ≤ 0.53 (AUC 0.99, 95% CI 0.96-1.00, P < 0.001), and ≤ 0.73 to predict late-onset preeclampsia (AUC 0.75, 95% CI 0.68-0.81, P < 0.001). Conclusion: Measuring first-trimester serum PAPP-A/PAPP-A2 ratio using the GO-SPR biosensor could be a valuable method for early prediction of preeclampsia.

The Current Status and Future Promise of SPR Biosensors.

The most commonly used protein detection methods in clinical diagnosis and disease monitoring are enzyme-linked immunosorbent assay (ELISA), Western blotting (immunoblot), and lateral flow assay (LFA) rapid screening, of which ELISA is the gold standard immunoassay in clinical practice [...].

Immunoassay-Amplified Responses Using a Functionalized MoS2-Based SPR Biosensor to Detect PAPP-A2 in Maternal Serum Samples to Screen for Fetal Down's Syndrome.

BACKGROUND: Due to educational, social and economic reasons, more and more women are delaying childbirth. However, advanced maternal age is associated with several adverse pregnancy outcomes, and in particular a high risk of Down's syndrome (DS). Hence, it is increasingly important to be able to detect fetal Down's syndrome (FDS). METHODS: We developed an effective, highly sensitive, surface plasmon resonance (SPR) biosensor with biochemically amplified responses using carboxyl-molybdenum disulfide (MoS2) film. The use of carboxylic acid as a surface modifier of MoS2 promoted dispersion and formed specific three-dimensional coordination sites. The carboxylic acid immobilized unmodified antibodies in a way that enhanced the bioaffinity of MoS2 and preserved biorecognition properties of the SPR sensor surface. Complete antigen pregnancy-associated plasma protein-A2 (PAPP-A2) conjugated with the carboxyl-MoS2-modified gold chip to amplify the signal and improve detection sensitivity. This heterostructure interface had a high work function, and thus improved the efficiency of the electric field energy of the surface plasmon. These results provide evidence that the interface electric field improved performance of the SPR biosensor. RESULTS: The carboxyl-MoS2-based SPR biosensor was used successfully to evaluate PAPP-A2 level for fetal Down's syndrome screening in maternal serum samples. The detection limit was 0.05 pg/mL, and the linear working range was 0.1 to 1100 pg/mL. The women with an SPR angle >46.57 m° were more closely associated with fetal Down's syndrome. Once optimized for serum Down's syndrome screening, an average recovery of 95.2% and relative standard deviation of 8.5% were obtained. Our findings suggest that carboxyl-MoS2-based SPR technology may have advantages over conventional ELISA in certain situations. CONCLUSION: Carboxyl-MoS2-based SPR biosensors can be used as a new diagnostic technology to respond to the increasing need for fetal Down's syndrome screening in maternal serum samples. Our results demonstrated that the carboxyl-MoS2-based SPR biosensor was capable of determining PAPP-A2 levels with acceptable accuracy and recovery. We hope that this technology will be investigated in diverse clinical trials and in real case applications for screening and early diagnosis in the future.

A Review of Graphene-Based Surface Plasmon Resonance and Surface-Enhanced Raman Scattering Biosensors: Current Status and Future Prospects.

The surface plasmon resonance (SPR) biosensor has become a powerful analytical tool for investigating biomolecular interactions. There are several methods to excite surface plasmon, such as coupling with prisms, fiber optics, grating, nanoparticles, etc. The challenge in developing this type of biosensor is to increase its sensitivity. In relation to this, graphene is one of the materials that is widely studied because of its unique properties. In several studies, this material has been proven theoretically and experimentally to increase the sensitivity of SPR. This paper discusses the current development of a graphene-based SPR biosensor for various excitation methods. The discussion begins with a discussion regarding the properties of graphene in general and its use in biosensors. Simulation and experimental results of several excitation methods are presented. Furthermore, the discussion regarding the SPR biosensor is expanded by providing a review regarding graphene-based Surface-Enhanced Raman Scattering (SERS) biosensor to provide an overview of the development of materials in the biosensor in the future.

Clinical Application for Screening Down's Syndrome by Using Carboxylated Graphene Oxide-Based Surface Plasmon Resonance Aptasensors.

BACKGROUND: Advanced medical detection technology requires high sensitivity and accuracy to increase the disease detection rate. We showed that carboxyl-functionalized graphene oxide (carboxyl-GO) biosensing materials are capable of accurate detection. METHODS: We developed a carboxylated GO-based surface plasmon resonance (SPR) aptasensor suitable for screening Down's syndrome in clinical serum. This biosensing material could rapidly and accurately detect hCG protein with a low concentration to identify fetal Down's syndrome. The developed carboxyl-GO-based SPR aptasensor showed excellent sensitivity and limit of detection without the use of antibodies and without any specific preference. RESULTS: hCG protein detection limits of 1 pM in buffer samples and 1.9 pM in clinical serum samples were achieved. The results showed that the carboxyl-GO-based chip could detect hCG well below the normal physiological level of serum protein (5.0 mIU/mL). High affinity, sensitivity, and better detection limit were obtained in the range of 1.9 pM to 135 pM. The results showed a 5k-fold dilution factor, and that an SPR angle shift of more than 20 millidegrees (mo) was associated with a significant risk of fetal Down's syndrome compared to normal pregnant women. The results clearly showed that the detection of hCG protein in serum samples from pregnant women at 12-19 weeks could be used to screen Down's syndrome with high selectivity and sensitivity. CONCLUSION: Our findings suggest the potential application of carboxyl-GO film in proof-of-concept studies for serum assays as a new type of SPR material. In addition, peptide and carboxyl-GO films may be conducive to the development of future point of care testing and rapid diagnostic devices for other diseases such as cancer.

Exploring Graphene and MoS2 Chips Based Surface Plasmon Resonance Biosensors for Diagnostic Applications.

Until now, two-dimensional (2D) nanomaterials have been widely studied and applied in the biosensor field. Some of the advantages offered by these 2D materials include large specific surface area, high conductivity, and easy surface modification. This review discusses the use of 2D material in surface plasmon resonance (SPR) biosensor for diagnostic applications. Two-dimensional material reviewed includes graphene and molybdenum disulfide (MoS2). The discussion begins with a brief introduction to the general principles of the SPR biosensor. The discussion continues by explaining the properties and characteristics of each material and its effect on the performance of the SPR biosensor, in particular its sensitivity. This review concludes with some recent applications of graphene- and MoS2-based SPR biosensor in diagnostic applications.

Simultaneous Real-Time Detection of Pregnancy-Associated Plasma Protein-A and -A2 Using a Graphene Oxide-Based Surface Plasmon Resonance Biosensor.

Background: Pregnancy-associated plasma protein-A and -A2 (PAPP-A and -A2) are principally expressed in placental trophoblasts and play a critical role in the regulation of fetal and placental growth. PAPP-A2 shares 45% amino acid similarity with PAPP-A. This study aimed to investigate the efficacy of real-time detection of PAPP-A and PAPP-A2 using a novel surface plasmon resonance (SPR) biosensor based on graphene oxide (GO). Methods: Traditional SPR and GO-based SPR chips were fabricated to measure PAPP-A and PAPP-A2 concentrations. We compared SPR response curves of PAPP-A and PAPP-A2 between traditional SPR and GO-SPR biosensors. We also performed interference tests and specificity analyses among PAPP-A, PAPP-A2, and mixed interference proteins. Results: The time to detect PAPP-A and PAPP-A2 was about 150 seconds with both traditional SPR and GO-SPR biosensors. Approximately double SPR angle shifts were noted with the GO-SPR biosensor compared to the traditional SPR biosensor at a PAPP-A and PAPP-A2 concentration of 5 µg/mL. The limit of detection of the GO-SPR biosensor was as low as 0.5 ng/mL for both PAPP-A and PAPP-A2. Interference testing revealed that almost all of the protein bonded on the GO-SPR biosensor with anti-PAPP-A from the mixture of proteins was PAPP-A, and that almost no other proteins were captured except for PAPP-A2. However, the SPR signal of PAPP-A2 (5.75 mdeg) was much smaller than that of PAPP-A (13.76 mdeg). Similar results were noted with anti-PAPP-A2, where almost all of the protein bonded on the GO-SPR biosensor was PAPP-A2. The SPR signal of PAPP-A (5.17 mdeg) was much smaller than that of PAPP-A2 (13.94 mdeg). Conclusion: The GO-SPR biosensor could distinguish PAPP-A and PAPP-A2 from various mixed interference proteins with high sensitivity and specificity. It could potentially be used to measure PAPP-A and PAPP-A2 in clinical blood samples during pregnancy.

High-Sensitivity Detection of the Lung Cancer Biomarker CYFRA21-1 in Serum Samples Using a Carboxyl-MoS2 Functional Film for SPR-Based Immunosensors.

We constructed a novel surface plasmon resonance (SPR) detection assay using carboxyl-functionalized molybdenum disulfide (carboxyl-MoS2) nanocomposites as a signal amplification sensing film for the ultrasensitive detection of the lung cancer-associated biomarker cytokeratin 19 fragment (CYFRA21-1). The experiment succeeded in MoS2 reacted with chloroacetic acid giving carboxyl-MoS2 as the reaction product. The additional shoulder in the C 1s and O 1s peaks of carboxyl-MoS2, which were increased in X-ray photoelectron spectroscopy, confirmed the presence of O-C=O groups on the surface of the carboxyl-MoS2. Compared to MoS2, the experimental results confirmed that carboxyl-modified MoS2 had improved low impedance and low refractive index. The carboxyl-MoS2-based chip had a high affinity, with an SPR angle shift enhanced by 2.6-fold and affinity binding K A enhanced by 15-fold compared to a traditional SPR sensor. The results revealed that the carboxyl-MoS2-based chip had high sensitivity, specificity, and SPR signal affinity, while the CYFRA21-1 assay in spiked clinical serum showed a lower detection limit of 0.05 pg/mL and a wider quantitation range (0.05 pg/mL to 100 ng/mL). The carboxyl-MoS2-based chip detection value was about 104 times more sensitive than the limit of detection of an enzyme-linked immunosorbent assay (ELISA) (0.60 ng/mL). The results showed that the carboxyl-MoS2-based chip had the potential to rapidly assay complex samples including bodily fluids, whole blood, serum, plasma, urine, and saliva in SPR-based immunosensors to diagnose diseases including cancer.

Development of a bioaffinity SPR immunosensor based on functionalized graphene oxide for the detection of pregnancy-associated plasma protein A2 in human plasma.

BACKGROUND: Graphene-like material such as functionalized carboxyl-graphene oxide (carboxyl-GO) can be intelligently tuned to achieve particular properties for biological and chemical sensing applications. METHODS: In this study, we propose a method to improve interference of non-specific proteins for use in human plasma assays. The highly specific interactions between molecules are an advantage of carboxyl-GO-based surface plasmon resonance (SPR) immunoassays, and this can be applied to spiked plasma samples with pregnancy-associated plasma protein A2 (PAPPA2). RESULTS: The experiment results showed that carboxyl-GO could be used to modulate the plasmon resonance energy, work function and conductivity properties. In addition, carboxyl groups could be used to enhance the conduction of electrons between carboxyl-GO and Au electrodes due to the excellent conductivity and electron transfer rate. The carboxyl-GO-based SPR chip exhibited high sensitivity based on the electric field amplification effects of the composite dielectric material. Therefore, the surface electric field could be enhanced by electron transfer, thereby greatly improving the sensitivity of the sensing system. Enhanced electric field intensity was generated around the carboxyl-GO of 63.58 V/m, and the measured work function was 4.95 eV. The results showed that the carboxyl-GO-based SPR biosensor had high sensitivity, affinity and selective ability for PAPPA2 protein with a high association rate constant (ka) of 3.1 ×109 M-1 S-1 and a limit of detection of 0.01 pg/mL in spiked human plasma. CONCLUSION: The results showed a detection accuracy of protein in spiked plasma of >90% compared to PBS buffer, suggesting that the carboxyl-GO-based SPR biosensor could be used in assays of human plasma for early and late gynecological diseases. The future of this technology will be useful for the diagnosis and evaluation of the risk of early maternal preeclampsia and potentially in clinical applications for gestational diseases.

High-affinity carboxyl-graphene oxide-based SPR aptasensor for the detection of hCG protein in clinical serum samples.

BACKGROUND: The use of functionalized graphene oxide (fGO) has led to a new trend in the sensor field, owing to its high sensitivity with regards to sensing characteristics and easy synthesis procedures. METHODS: In this study, we developed an ultra-sensitive carboxyl-graphene oxide (carboxyl-GO)-based surface plasmon resonance (SPR) aptasensor using peptides to detect human chorionic gonadotropin (hCG) in clinical serum samples. The carboxyl-GO based SPR aptasensor provided high affinity and stronger binding of peptides, which are great importance to allow for a non-immunological label-free mechanism. Also, it allows the detection of low concentrations of hCG, which are in turn considered to be important clinical parameters to diagnose ectopic pregnancies and paraneoplastic syndromes. RESULTS: The high selectivity of the carboxyl-GO-based SPR aptasensor for hCG recombinant protein was verified by the addition of the interfering proteins bovine serum albumin (BSA) and human serum albumin (HSA), which did not affect the sensitivity of the sensor. The carboxyl-GO-based chip can enhance the assay efficacy of interactions between peptides and had a high affinity binding for a ka of 17×106 M-1S-1. The limit of detection for hCG in clinical serum samples was 1.15 pg/mL. CONCLUSION: The results of this study demonstrated that the carboxyl-GO-based SPR aptasensor had excellent sensitivity, affinity and selectivity, and thus the potential to be used as disease-related biomarker assay to allow for an early diagnosis, and possibly a new area in the field of biochemical sensing technology.

Affinity capture surface carboxyl-functionalized MoS2 sheets to enhance the sensitivity of surface plasmon resonance immunosensors.

The development of functionalized molybdenum disulfide (MoS2) has led to a new trend in the biosensing field, owing to its high sensitivity and bio-affinity characteristics with regards to the simple synthesis of carboxyl-functionalized MoS2 nanocomposites. In this study, we used monochloroacetic acid (MCA) to successfully modify carboxyl-MoS2. The efficiency of this MCA modification method showed a higher -COOH group content of 30.1%, mainly due to chlorine atoms occupying the MoS2 sulfur vacancy to allow for the formation of a strong bonding effect. This then enhanced the surface area of -COOH and improved the formation of covalent bonds between proteins. We demonstrated that MoS2-COOH-based surface plasmon resonance (SPR) chips can provide excellent sensitivity and high affinity for immunoassay biomolecules detected in a low sample volume of 20 µl. With respect to the shifts of the SPR angles of the chips, the high binding affinity at a BSA concentration of 14.5 nM for a MoS2-COOH chip, a MoS2 chip and a traditional SPR chip are 4.69 m°, 2.49 m° and 1.53 m°, respectively. In addition, the MoS2-COOH chip could amplify the SPR angle response by 3.1 folds and enhance the high association rate of ka by 212 folds compared to MoS2 and traditional SPR chips. The results thus obtained revealed that the overall affinity binding value, KA, of the MoS2-COOH chip can be significantly enhanced by up to ∼ 6.5 folds that of the MoS2 chip. In summary, the excellent binding affinity, biocompatible and high sensitivity suggest the potential of the clinical application of this MoS2-COOH-based SPR chip detection method for in vitro diagnostic and point-of-care testing devices.

Enhanced Plasmonic Biosensors of Hybrid Gold Nanoparticle-Graphene Oxide-Based Label-Free Immunoassay.

In this study, we propose a modified gold nanoparticle-graphene oxide sheet (AuNP-GO) nanocomposite to detect two different interactions between proteins and hybrid nanocomposites for use in biomedical applications. GO sheets have high bioaffinity, which facilitates the attachment of biomolecules to carboxyl groups and has led to its use in the development of sensing mechanisms. When GO sheets are decorated with AuNPs, they introduce localized surface plasmon resonance (LSPR) in the resonance energy transfer of spectral changes. Our results suggest a promising future for AuNP-GO-based label-free immunoassays to detect disease biomarkers and rapidly diagnose infectious diseases. The results showed the detection of antiBSA in 10 ng/ml of hCG non-specific interfering protein with dynamic responses ranging from 1.45 nM to 145 fM, and a LOD of 145 fM. Considering the wide range of potential applications of GO sheets as a host material for a variety of nanoparticles, the approach developed here may be beneficial for the future integration of nanoparticles with GO nanosheets for blood sensing. The excellent anti-interference characteristics allow for the use of the biosensor in clinical analysis and point-of-care testing (POCT) diagnostics of rapid immunoassay products, and it may also be a potential tool for the measurement of biomarkers in human serum.

Real-time and stepwise deoxidization processes to tune the photoluminescence properties of graphene oxide using EC-SPR spectroscopy.

The development of a stepwise deoxidized process and real-time monitoring of the large-scale mass production of electrochemically reduced graphene oxide (ErGO) sheets are important issues. In this study, we have shown that graphene oxide (GO) sheets can be quantitatively monitored in real-time and controlled in a stepwise manner using electrochemical-surface plasmon resonance (EC-SPR), due to the fact that the oxygen functional groups can be tuned through a deoxidization procedure. The SPR signal can then be detected quantitatively in real-time by changes in the dielectric constant of the GO film during the EC stepwise removal of oxygen functional groups. This is because the refractive index of the GO sheets is affected by the oxygen-containing groups, so that monitoring the SPR angle shift provides a real-time measure of changes in the concentration of the residual oxygen functional groups of the GO sheets. In this study, we demonstrated GO and 100 CV cycles of ErGO at X-ray photoelectron spectroscopy carbon-to-oxygen ratios of 4.1 and 31.57 respectively, and Raman spectra of the D/G intensity ratio of 0.85 and 1.89, respectively. The 100 CV cycles of ErGO at SPR angle shifts were -227.13 mdeg for GO at a concentration of 0.275 mg ml-1, and -263.47 mdeg for GO at a concentration of 1 mg ml-1. The photoluminescence emission bands of the GO and the CV 100 cycles of ErGO were 615 to 470 nm. These results may be beneficial for future studies on GO fluorescence characteristics in the field of optoelectronic and biosensor applications.

Ultra-high sensitivity of the non-immunological affinity of graphene oxide-peptide-based surface plasmon resonance biosensors to detect human chorionic gonadotropin.

Specific peptide aptamers can be used in place of expensive antibody proteins, and they are gaining increasing importance as sensing probes due to their potential in the development of non-immunological assays with high sensitivity, affinity and specificity for human chorionic gonadotropin (hCG) protein. We combined graphene oxide (GO) sheets with a specific peptide aptamer to create a novel, simple and label-free tool to detect abnormalities at an early stage of pregnancy, a GO-peptide-based surface plasmon resonance (SPR) biosensor. This is the first binding interface experiment to successfully demonstrate binding specificity in kinetic analysis biomechanics in peptide aptamers and GO sheets. In addition to the improved affinity offered by the high compatibility with the target hCG protein, the major advantage of GO-peptide-based SPR sensors was their reduced nonspecific adsorption and enhanced sensitivity. The calculation of total electric field intensity (ΔE) in the GO-based sensing interfaces was significantly enhanced by up to 1.2 times that of a conventional SPR chip. The GO-peptide-based chip (1mM) had a high affinity (KA) of 6.37×1012M-1, limit of detection of 0.065nM and ultra-high sensitivity of 16 times that of a conventional SPR chip. The sensitivity of the slope ratio of the low concentration hCG protein assay in linear regression analysis was GO-peptide (1mM): GO-peptide (0.1mM): conventional chip (8-mercaptooctanoic acid)-peptide (0.1mM)=8.6: 3.3: 1. In summary, the excellent binding affinity, low detection limit, high sensitivity, good stability and specificity suggest the potential of this GO-peptide-based SPR chip detection method in clinical application. The development of real-time whole blood analytic and diagnostic tools to detect abnormalities at an early stage of pregnancy is a promising technique for future clinical application.

Carboxyl-functionalized graphene oxide composites as SPR biosensors with enhanced sensitivity for immunoaffinity detection.

This work demonstrates the excellent potential of carboxyl-functionalized graphene oxide (GO-COOH) composites to form biocompatible surfaces on sensing films for use in surface plasmon resonance (SPR)-based immunoaffinity biosensors. Carboxyl-functionalization of graphene carbon can modulate its visible spectrum, and can therefore be used to improve and control the plasmonic coupling mechanism. The binding properties of the molecules between a sensing film and a protein were elucidated at various flow rates of those molecules. The bio-specific binding interaction among the molecules was investigated by performing an antigen and antibody affinity immunoassay. The results thus obtained revealed that the overall affinity binding value, KA, of the Au/GO-COOH chip can be significantly enhanced by up to ∼5.15 times that of the Au/GO chip. With respect to the shifts of the SPR angles of the chips, the affinity immunoassay interaction at a BSA concentration of 1µg/ml for an Au/GO-COOH chip, an Au/GO chip and a traditional SPR chip are 35.5m°, 9.128m° and 8.816m°, respectively. The enhancement of the antigen-antibody interaction of the Au/GO-COOH chip cause this chip to become four times as sensitive to the SPR angle shift and to have the lowest antibody detection limit of 0.01pg/ml. These results indicate the potential of the chip in detecting specific proteins, and the development of real-time in vivo blood analysis and diagnosis based on cancer tumor markers.

Enhancing extraction of light from metal composite structures for plasmonic emitters using light-coupling effect.

This work demonstrates the efficiency and directionality of a method of extracting light from thin-film emissive devices by near-field evanescent waves in plasmonic emitters used in metal composite grating structures. A near-field evanescent wave can induce a surface plasmon wave on the surface of a metal under resonant conditions. Enhancing the near-field evanescent wave generates strong far-field nonlinear optical effects. This effect is highly efficient in some plasmonic emitter structures. Theoretical and experimental results demonstrate that such a metal composite grating structure exhibits good performance, a high coupling ratio, a small coupling angle, enhanced light extraction and a small FWHM. It also improves luminous efficiency, emitter angle, and directivity.

Graphene oxide-based SPR biosensor chip for immunoassay applications.

This work develops a highly sensitive immunoassay sensor for use in graphene oxide sheet (GOS)-based surface plasmon resonance (SPR) chips. This sensing film, which is formed by chemically modifying a GOS surface, has covalent bonds that strongly interact with the bovine serum albumin (BSA), explaining why it has a higher sensitivity. This GOS film-based SPR chip has a BSA concentration detection limit that is 100 times higher than that of the conventional Au-film-based sensor. The affinity constants (K A) on the GOS film-based SPR chip and the conventional SPR chip for 100 µg/ml BSA are 80.82 × 10(6) M(-1) and 15.67 × 10(6) M(-1), respectively. Therefore, the affinity constant of the GOS film-based SPR chip is 5.2 times higher than that of the conventional chip. With respect to the protein-protein interaction, the SPR sensor capability to detect angle changes at a low concentration anti-BSA of 75.75 nM on the GOS film-based SPR chip and the conventional SPR chip is 36.1867 and 26.1759 mdeg, respectively. At a high concentration, anti-BSA of 378.78 nM on the GOS film-based SPR chip and the conventional SPR chip reveals two times increases in the SPR angle shift. Above results demonstrate that the GOS film is promising for highly sensitive clinical diagnostic applications.

Enhanced sensitivity of anti-symmetrically structured surface plasmon resonance sensors with zinc oxide intermediate layers.

We report a novel design wherein high-refractive-index zinc oxide (ZnO) intermediary layers are used in anti-symmetrically structured surface plasmon resonance (SPR) devices to enhance signal quality and improve the full width at half maximum (FWHM) of the SPR reflectivity curve. The surface plasmon (SP) modes of the ZnO intermediary layer were excited by irradiating both sides of the Au film, thus inducing a high electric field at the Au/ZnO interface. We demonstrated that an improvement in the ZnO (002) crystal orientation led to a decrease in the FWHM of the SPR reflectivity curves. We optimized the design of ZnO thin films using different parameters and performed analytical comparisons of the ZnO with conventional chromium (Cr) and indium tin oxide (ITO) intermediary layers. The present study is based on application of the Fresnel equation, which provides an explanation and verification for the observed narrow SPR reflectivity curve and optical transmittance spectra exhibited by (ZnO/Au), (Cr/Au), and (ITO/Au) devices. On exposure to ethanol, the anti-symmetrically structured showed a huge electric field at the Au/ZnO interface and a 2-fold decrease in the FWHM value and a 1.3-fold larger shift in angle interrogation and a 4.5-fold high-sensitivity shift in intensity interrogation. The anti-symmetrically structured of ZnO intermediate layers exhibited a wider linearity range and much higher sensitivity. It also exhibited a good linear relationship between the incident angle and ethanol concentration in the tested range. Thus, we demonstrated a novel and simple method for fabricating high-sensitivity, high-resolution SPR biosensors that provide high accuracy and precision over relevant ranges of analyte measurement.