Surface Plasmon Resonance-based Biosensor Research Articles

Classical and Quantum Surface Plasmon Resonance Biosensing

Surface plasmon resonance is an optical phenomenon first discovered in 1902. The phenomenon has since had many applications, particularly in biosensing. In this paper, we review surface plasmon resonance-based biosensing, look at recent progress made in integrating quantum resources to develop surface plasmon resonance-based biosensors into a class of surface plasmon resonance biosensors commonly referred to as quantum surface plasmon resonance biosensors, and examine the advantages which quantum biosensors bring. We will review recent experimental and theoretical work showing that making use of quantum states of light offers a great enhancement in the precision of our biosensor, as they can go below the shot-noise limit (standard quantum limit) of precision in intensity noise detection. An overview of the surface plasmon resonance mechanism, its applications, and some limitations, as well as a report on recent research to address certain limitations and quantum-based surface plasmon resonance sensing, are provided.

Numerical Study of Titanium Dioxide and MXene Nanomaterial-Based Surface Plasmon Resonance Biosensor for Virus SARS-CoV-2 Detection.

A novel surface plasmon resonance-based biosensor for SARS-CoV-2 virus is proposed in this article. The biosensor is a Kretschmann configuration-based structure that consists of CaF2 prism as base, at which silver (Ag), TiO2, and MXene nanolayers are used to enhance the performance. Theoretically, the performance parameters have been investigated by means of Fresnel equations and transfer matrix method (TMM). The TiO2 nanolayer not only prevents oxidation of Ag layer but also enhances the evanescent field in its vicinity. The sensor provides an ultrahigh angular sensitivity of 346°/RIU for the detection of SARS-CoV-2 virus. Some other performance parameters, including FWHM (full width at half maxima), detection accuracy (DA), limit of detection (LOD), and quality factor (QF) have also been calculated for proposed SPR biosensor with their optimized values 2.907°, 0.3439deg-1, 1.445 × 10-5, and 118.99 RIU-1, respectively. The obtained results designate that the proposed surface plasmon resonance (SPR) based biosensor has notably enhanced angular sensitivity as compared to previous results reported in the literatures till date. This work may facilitate a significant biological sample sensing device for fast and accurate diagnosis at early stage of SARS-CoV-2 virus.

Wearable Localized Surface Plasmon Resonance-Based Biosensor with Highly Sensitive and Direct Detection of Cortisol in Human Sweat

Wearable biosensors have the potential for developing individualized health evaluation and detection systems owing to their ability to provide continuous real-time physiological data. Among various wearable biosensors, localized surface plasmon resonance (LSPR)-based wearable sensors can be versatile in various practical applications owing to their sensitive interactions with specific analytes. Understanding and analyzing endocrine responses to stress is particularly crucial for evaluating human performance, diagnosing stress-related diseases, and monitoring mental health, as stress takes a serious toll on physiological health and psychological well-being. Cortisol is an essential biomarker of stress because of the close relationship between cortisol concentration in the human body and stress level. In this study, a flexible LSPR biosensor was manufactured to detect cortisol levels in the human body by depositing gold nanoparticle (AuNP) layers on a 3-aminopropyltriethoxysilane (APTES)-functionalized poly (dimethylsiloxane) (PDMS) substrate. Subsequently, an aptamer was immobilized on the surface of the LSPR substrate, enabling highly sensitive and selective cortisol capture owing to its specific cortisol recognition. The biosensor exhibited excellent detection ability in cortisol solutions of various concentrations ranging from 0.1 to 1000 nM with a detection limit of 0.1 nM. The flexible LSPR biosensor also demonstrated good stability under various mechanical deformations. Furthermore, the cortisol levels of the flexible LSPR biosensor were also measured in the human epidermis before and after exercise as well as in the morning and afternoon. Our biosensors, which combine easily manufactured flexible sensors with sensitive cortisol-detecting molecules to measure human stress levels, could be versatile candidates for human-friendly products.

Classification Learning Assisted Biosensor Data Analysis for Preemptive Plant Disease Detection

In the agricultural sector, identifying plant diseases is crucial as they hamper the plant's robustness and health, which play a vital role in agricultural productivity. Early detection allows farmers to take proper measurements and save crops from complete failure. Biosensor applications in agricultural production and plant monitoring improve the yield through definitive recommendations and improved practices. Fluorescence-based assays, colorimetric biosensors, and surface plasmon resonance-based biosensors are the most commonly used for plant pathogen detection. Plant disease detection is a prime biosensor application for preventing seasonal and cultural defects in raising crops. The sensor data analysis ensures reliable processing for distinguishable features for identifying the disease, wherein discrete information is handled with error. This article introduces a Preemptive Classification using Discrete Data (PC-DD) technique to resolve this issue. This technique requires partial series through probabilistic data substitution to improve the analysis rate. In the analysis process, the classification is performed using random forest based on two combinations: series, difference, and probability. This probability is based on identical data observed through series probability classification in the previous iteration. The unidentical data is classified under difference that is used for individual classification. This process is progressive until the detection is performed, wherein the alterations are adaptable for different biosensor input data. Therefore, the proposed technique's performance is validated using the metrics detection accuracy, analysis ratio, analysis time, classifications, and difference factor.

Localized surface plasmon resonance-based biosensor on gold nanoparticles for Taenia solium detection

This paper describes, for the first time to our knowledge, a fast-response and specific biosensor for detection of Taenia solium, a parasite responsible for neurocysticercosis disease that affects the central nervous system. The biosensor is based on the localized surface plasmon resonance (LSPR) technique on gold nanoparticles (AuNPs) in colloidal suspension that were functionalized and activated with antibodies to perform an immuno-capture effect. The AuNPs were synthetized by Turkevich and seed-mediated growth methods. A variety of concentrations of T. solium antigen were added to test the detection and the dose-response profile. Small antigen concentrations were detected indicating that the limit of detection is lower than 0.1 µg/mL of antigen. The results demonstrate the potential of the AuNPs LSPR biosensor as a clinical tool for neurocysticercosis diagnostic.

Nano-layered surface plasmon resonance-based highly sensitive biosensor for virus detection: A theoretical approach to detect SARS-CoV-2.

The outbreak of the coronavirus disease (COVID-19) pandemic has become a worldwide health catastrophe instigated by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Countries are battling to slow the spread of this virus by testing and treating patients, along with other measures such as prohibiting large gatherings, maintaining social distance, and frequent, thorough hand washing, as no vaccines or medicines are available that could effectively treat infected people for different types of SARS-CoV-2 variants. However, the testing procedure to detect this virus is lengthy. This study proposes a surface plasmon resonance-based biosensor for fast detection of SARS-CoV-2. The sensor employs a multilayered configuration consisting of TiO2–Ag–MoSe2 graphene with a BK7 prism. Antigen–antibody interaction was considered the principle for this virus detection. Immobilized CR3022 antibody molecules for detecting SARS-CoV-2 antigens (S-glycoprotein) are used for this sensor. It was found that the proposed sensor’s sensitivity (194°/RIU), quality factor (54.0390 RIU−1), and detection accuracy (0.2702) outperformed those of other single and multilayered structures. This study could be used as a theoretical base and primary step in constructing an actual sensor.

Screening and Identification of Herbal Urease Inhibitors Using Surface Plasmon Resonance Biosensor

Background and objectives: Urease, that catalyzes the hydrolysis of urea, has received substantial attention for its impact on living organisms’ health and human life quality. Urease inhibitors play important role in management of different diseases including gastritis and other gastrointestinal disorders. In the present study, a new surface plasmon resonance-based biosensor was designed to discover new urease inhibitors. Methods: The biosensor surface was prepared by the covalent immobilization of urease on carboxymethyldextran hydrogel (CMD 500D) via its primary amine groups. Results: The biosensor combined with an orthogonal enzyme inhibition assay was utilized for screening of 40 traditional medicinal plant extracts against Jack-bean urease. Among them, Laurus nobilis leaf extract displayed a high affinity with the immobilized urease; therefore, its active compound (quercetin) was isolated and identified as a urease inhibitor. The equilibrium constant (KD) and Gibbs free energy (ΔGbinding) values for the interaction of quercetin with urease were obtained to be 55 nM and -41.62 kJ/mol, respectively. The results of molecular docking analysis also confirmed our findings. Conclusion: This SPR-based biosensor represents a new, fast, reliable, and an accurate technique for the identification of new urease inhibitors or novel 'lead' compounds from natural resources.

Determination of the composition of heterogeneous binder solutions by surface plasmon resonance biosensing

Surface plasmon resonance-based biosensors have been extensively applied to the characterization of the binding kinetics between purified (bio)molecules, thanks to robust data analysis techniques. However, data analysis for solutions containing multiple interactants is still at its infancy. We here present two algorithms for (1) the reliable and accurate determination of the kinetic parameters of N interactants present at different ratios in N mixtures and (2) the estimation of the ratios of each interactant in a given mixture, assuming that their kinetic parameters are known. Both algorithms assume that the interactants compete to bind to an immobilized ligand in a 1:1 fashion and necessitate prior knowledge of the total concentration of all interactants combined. The effectiveness of these two algorithms was experimentally validated with a model system corresponding to mixtures of four small molecular weight drugs binding to an immobilized protein. This approach enables the in-depth characterization of mixtures using SPR, which may be of considerable interest for many drug discovery or development applications, notably for protein glycovariant analysis.

Nanotechnology-Based Approaches for the Detection of SARS-CoV-2

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as a pandemic has been validated as an extreme clinical calamity and has affected several socio-economic activities globally. Proven transmission of this virus occurs through airborne droplets from an infected person. The recent upsurge in the number of infected individuals has already exceeded the number of intensive care beds available to patients. These extraordinary circumstances have elicited the need for the development of diagnostic tools for the detection of the virus and, hence, prevent the spread of the disease. Early diagnosis and effective immediate treatment can reduce and prevent an increase in the number of cases. Conventional methods of detection such as quantitative real-time polymerase chain reaction and chest computed tomography scans have been used extensively for diagnostic purposes. However, these present several challenges, including prolonged assay requirements, labor-intensive testing, low sensitivity, and unavailability of these resources in remote locations. Such challenges urgently require fast, sensitive, and accurate diagnostic techniques for the timely detection and treatment of coronavirus disease 2019 (COVID-19) infections. Point-of-care biosensors that include paper- and chip-based diagnostic systems are rapid, cost-effective, and user friendly. In this article nanotechnology-based potential biosensors for SARS-CoV-2 diagnosis are discussed with particular emphasis on a lateral flow assay, a surface-enhanced Raman scattering-based biosensor, a localized surface plasmon resonance-based biosensor, Förster resonance energy transfer, an electrochemical biosensor, and artificial intelligence-based biosensors. Several biomolecules, such as nucleic acids, antibodies/enzymes, or aptamers, can serve as potential detection molecules on an appropriate platform, such as graphene oxide, nanoparticles, or quantum dots. An effective biosensor can be developed by using appropriate combinations of nanomaterials and technologies.

Optimization of surface plasmon resonance-based biosensors for monitoring hemoglobin levels in human blood

Biological sensors based on surface plasmon resonance (SPR) are used in a wide range of fields such as pharmacy, medicine, food and drink safety to measure biological and chemical parameters. These sensors function by detecting changes in the refractive index of the sample environment. In this paper a biosensor design based on surface Plasmon resonance is introduced for the purpose of monitoring hemoglobin concentrations in human blood. Our design is based on a Kretschmann structure which contains an SF10 prism, with metal, graphene and metal dichalcogenide layers. The optical source considered here is a He–Ne laser with the wavelength of 632.8 nm. The effect of adding graphene and metal dichalcogenide layers to the structure of these sensors has been investigated. Our investigation of this structure shows that depending on the specific structure of metal dichalcogenide, the addition of this layer increases the sensitivity of the sensor. Using this optimized structure, our main goal of a blood health monitoring device can be achieved. We use this structure to determine the reflection coefficients that correspond with the healthy range of hemoglobin concentration in human blood based on the refractive index of human blood. This sensor is first optimized for sensitivity using water as a sample, this optimized sensor is then used to investigate the range of human blood in a healthy state of blood iron for men and women between the ages of 20 until 80 years. Results show that the reflection coefficients of the optimized structure for healthy range of hemoglobin concentrations for an adult man is from 0.6805(a.u) to 0.7067(a.u) and for an adult female is from 0.6547(a.u) to 0.6583(a.u).

Highly sensitive and selective localized surface plasmon resonance biosensor for detecting glutamate realized on optical fiber substrate using gold nanoparticles

In this study, we fabricated and characterized a localized surface plasmon resonance-based biosensor comprising gold nanoparticles (AuNPs) on an optical fiber substrate to detect glutamate at concentrations ranging from 0 to 10 mM. To fabricate the probe, AuNPs were decorated on an unclad portion of an optical fiber, and the enzyme glutamate dehydrogenase and coenzyme nicotinamide adenine dinucleotide were co-immobilized over the AuNPs. The sensor was designed to operate according to an intensity modulation scheme where the absorbance changed as the glutamate concentration varied in the sample around the probe. The change in the absorbance was due to the chemical reaction between glutamate dehydrogenase, glutamate, water and NAD+ which affected the refractive index of the medium around the AuNPs. The changes in the local refractive index led to significant variations in the absorbance of the AuNPs present in the sensing layer. The change recorded in the absorbance by AuNPs was 0.019 for the glutamate concentration range from 0 to 10 mM. The limit of detection and sensitivity of the sensor were determined as 0.36 mM and 0.0048 AU/mM, respectively. The sensor has advantages in terms of its low cost, immunity to electromagnetic interference, miniaturized probe, and capability of online monitoring and remote sensing because an optical fiber is used as the substrate for probe fabrication.

Sensitivity enhancement of surface plasmon resonance biosensor based on graphene and barium titanate layers

A surface plasmon resonance-based biosensor, consisting prism, silver, barium titanate (BaTiO3) and graphene layers, is presented by using angular interrogation. The structure is specially designed to further enhance the sensitivity and to decrease the full width at half maximum (FWHM) thereby improving the sensor performance. Theoretical analysis shows that the highest sensitivity can reach at 257°/RIU where the thickness of Ag layer is 45 nm with 10 nm BaTiO3 and one graphene layer. Compared with existing biosensors, the proposed biosensor exhibits higher sensitivity, lower FWHM and two times better preformation in the quality factor of the sensor, which would make our design have more applications in the field of biosensors.

An Immuno-Biochip Selectively Captures Tumor-Derived Exosomes and Detects Exosomal RNAs for Cancer Diagnosis.

Tumor-derived exosomes (TEXs) play instrumental roles in tumor growth, angiogenesis, immune modulation, metastasis, and drug resistance. TEX RNAs are a new class of noninvasive biomarkers for cancer. Neither current techniques, such as quantitative reverse transcription polymerase chain reaction (qRT-PCR) and next-generation sequencing, nor new ones, such as electrochemical or surface plasmon resonance-based biosensors, are able to selectively capture and separate TEXs from normal cell-derived exosomes, making TEX RNAs potentially less sensitive biomarkers. We developed an immuno-biochip that selectively captures TEXs using antibodies against tumor-associated proteins and quantifies in situ TEX RNAs using cationic lipoplexes containing molecular beacons. We used the immuno-biochip to measure the expression of miR-21 microRNA and TTF-1 mRNA in EGFR- or PD-L1-bearing exosomes from human sera and achieved absolute sensitivity and specificity in distinguishing normal controls from non-small cell lung cancer patients. Our results demonstrated that the effective separation of TEXs from other exosomes greatly improved the detection sensitivity and specificity. Compared with the traditional immunomagnetic separation-RNA isolation-qRT-PCR workflow, the immuno-biochip showed superior lung cancer diagnostic performance, consumed less samples (∼30 μL), and shortened assay time from ∼24 to 4 h.

Label-Free Detection of Tear Biomarkers Using Hydrogel-Coated Gold Nanoshells in a Localized Surface Plasmon Resonance-Based Biosensor.

The dependence of the localized surface plasmon resonance (LSPR) of noble-metal nanomaterials on refractive index makes LSPR a useful, label-free signal transduction strategy for biosensing. In particular, by decorating gold nanomaterials with molecular recognition agents, analytes of interest can be trapped near the surface, resulting in an increased refractive index surrounding the nanomaterial, and, consequently, a red shift in the LSPR wavelength. Ionic poly( N-isopropylacrylamide- co-methacrylic acid) (PNM) hydrogels were used as protein receptors because PNM nanogels exhibit a large increase in refractive index upon protein binding. Specifically, PNM hydrogels were synthesized on the surface of silica gold nanoshells (AuNSs). This composite material (AuNS@PNM) was used to detect changes in the concentration of two protein biomarkers of chronic dry eye: lysozyme and lactoferrin. Both of these proteins have high isoelectric points, resulting in electrostatic attraction between the negatively charged PNM hydrogels and positively charged proteins. Upon binding lysozyme or lactoferrin, AuNS@PNM exhibits large, concentration-dependent red shifts in LSPR wavelength, which enabled the detection of clinically relevant concentration changes of both biomarkers in human tears. The LSPR-based biosensor described herein has potential utility as an affordable screening tool for chronic dry eye and associated conditions.

SPRi-Based Biosensing Platforms for Detection of Specific DNA Sequences Using Thiolate and Dithiocarbamate Assemblies.

The framework of presented study covers the development and examination of the analytical performance of surface plasmon resonance-based (SPR) DNA biosensors dedicated for a detection of model target oligonucleotide sequence. For this aim, various strategies of immobilization of DNA probes on gold transducers were tested. Besides the typical approaches: chemisorption of thiolated ssDNA (DNA-thiol) and physisorption of non-functionalized oligonucleotides, relatively new method based on chemisorption of dithiocarbamate-functionalized ssDNA (DNA-DTC) was applied for the first time for preparation of DNA-based SPR biosensor. The special emphasis was put on the correlation between the method of DNA immobilization and the composition of obtained receptor layer. The carried out studies focused on the examination of the capability of developed receptors layers to interact with both target DNA and DNA-functionalized AuNPs. It was found, that the detection limit of target DNA sequence (27 nb length) depends on the strategy of probe immobilization and backfilling method, and in the best case it amounted to 0.66 nM. Moreover, the application of ssDNA-functionalized gold nanoparticles (AuNPs) as plasmonic labels for secondary enhancement of SPR response is presented. The influence of spatial organization and surface density of a receptor layer on the ability to interact with DNA-functionalized AuNPs is discussed. Due to the best compatibility of receptors immobilized via DTC chemisorption: 1.47 ± 0.4 · 1012 molecules · cm−2 (with the calculated area occupied by single nanoparticle label of ~132.7 nm2), DNA chemisorption based on DTCs is pointed as especially promising for DNA biosensors utilizing indirect detection in competitive assays.

Novel mouse monoclonal antibodies specifically recognize Aspergillus fumigatus galactomannan.

A panel of specific monoclonal antibodies (mAbs) against synthetic pentasaccharide β-D-Galf-(1→5)-[β-D-Galf-(1→5)]3-α-D-Manp, structurally related to Aspergillus fumigatus galactomannan, was generated using mice immunized with synthetic pentasaccharide-BSA conjugate and by hybridoma technology. Two selected mAbs, 7B8 and 8G4, could bind with the initial pentasaccharide with affinity constants of approximately 5.3 nM and 6.4 nM, respectively, based on surface plasmon resonance-based biosensor assay. The glycoarray, built from a series of synthetic oligosaccharide derivatives representing different galactomannan fragments, demonstrated that mAb 8G4 could effectively recognize the parental pentasaccharide while mAb 7B8 recognizes its constituting trisaccharide parts. Immunofluorescence studies showed that both 7B8 and 8G4 could stain A. fumigatus cells in culture efficiently, but not the mutant strain lacking galactomannan. In addition, confocal microscopy demonstrated that Candida albicans, Bifidobacterium longum, Lactobacillus plantarum, and numerous gram-positive and gram-negative bacteria were not labeled by mAbs 7B8 and 8G4. The generated mAbs can be considered promising for the development of a new specific enzyme-linked assay for detection of A. fumigatus, which is highly demanded for medical and environmental controls.

Isatin-induced increase in the affinity of human ferrochelatase and adrenodoxin reductase interaction.

Isatin (indol-2,3-dione) is an endogenous non-peptide regulator exhibiting a wide range of biological and pharmacological activities, which are poorly characterized in terms of their molecular mechanisms. Identification of many isatin-binding proteins in the mammalian brain and liver suggests that isatin may influence their functions. We have hypothesized that besides direct action on particular protein targets, isatin can act as a regulator of protein-protein interactions (PPIs). In this surface plasmon resonance-based biosensor study we have found that physiologically relevant concentrations of isatin (25-100 μM) increase affinity of interactions between human recombinant ferrochelatase (FECH) and NADPH-dependent adrenodoxin reductase (ADR). In the presence of increasing concentrations of isatin the Kd values demonstrated a significant (up to 6-fold) decrease. It is especially important that the interaction of isatin with each individual protein (FECH, ADR) was basically negligible and therefore could not contribute to the observed effect. This effect was specific only for the FECH/ADR complex formation and was not observed for other protein complexes studied: FECH/cytochrome b5(CYB5A) and FECH/SMAD4.

Quantification and simultaneous evaluation of the bioactivity of antibody produced in CHO cell culture-The use of the ectodomain of FcγRI and surface plasmon resonance-based biosensor.

A surface plasmon resonance (SPR)-based assay has been developed in order to quantify the monoclonal antibody (Mab) Trastuzumab within the supernatant of a mammalian cell culture using the ectodomain of FcγRI (CD64) and confirm Mab bioactivity, i.e. binding to its antigen Her2, in a single biosensing experiment. Under partial mass transport limitation, we were able to quantify Mab present in unpurified samples taken throughout the cell culture. While Mab capture on the biosensor surface confirmed the ability of its Fc region to bind to FcγRI, the binding activity of its Fab region was also tested by injecting increasing concentrations of the Mab antigen (Her2). The kinetics of the interactions we recorded from 48h post transfection until the end of the culture, were superimposable, which highly suggested that the quality attributes of the antibody were conserved throughout the process. This SPR methodology is thus of great interest for atline quality control analysis during Mab production campaign.

Moderate to high throughput in vitro binding kinetics for drug discovery.

This review provides a concise summary for state of the art, moderate to high throughput in vitro technologies being employed to study drug-target binding kinetics. These technologies cover a wide kinetic timescale spanning up to nine orders of magnitude from milliseconds to days. Automated stopped flow measures transient and (pre)steady state kinetics from milliseconds to seconds. For seconds to hours timescale kinetics we discuss surface plasmon resonance-based biosensor, global progress curve analysis for high throughput kinetic profiling of enzyme inhibitors and activators, and filtration plate-based radioligand or fluorescent binding assays for receptor binding kinetics. Jump dilution after pre-incubation is the preferred method for very slow kinetics lasting for days. The basic principles, best practices and simulated data for these technologies are described. Finally, the application of a universal label-free technology, liquid chromatography coupled tandem mass spectrometry (LC/MS/MS), is briefly reviewed. Select literature referencesare highlighted for in-depth understanding. A new reality is dawning wherein binding kinetics is an integral and routine part of mechanism of action elucidation and translational, quantitative pharmacology for drug discovery.

Complementary DNA display selection of high-affinity peptides binding the vacuolating toxin (VacA) of Helicobacter pylori.

Artificial peptides designed for molecular recognition of a bacterial toxin have been developed. Vacuolating cytotoxin A protein (VacA) is a major virulence factor of Helicobacter pylori, a gram-negative microaerophilic bacterium inhabiting the upper gastrointestinal tract, particularly the stomach. This study attempted to identify specific peptide sequences with high affinity for VacA using systematic directed evolution in vitro, a cDNA display method. A surface plasmon resonance-based biosensor and fluorescence correlation spectroscopy to examine binding of peptides with VacA identified a peptide (GRVNQRL) with high affinity. Cyclization of the peptide by attaching cysteine residues to both termini improved its binding affinity to VacA, with a dissociation constant (Kd ) of 58 nm. This study describes a new strategy for the development of artificial functional peptides, which are promising materials in biochemical analyses and medical applications.