Sensitive Surface Plasmon Resonance Biosensor Research Articles

A sensitive SPR biosensor based on hollow gold nanospheres and improved sandwich assay with PDA-Ag@Fe3O4/rGO

A novel surface plasmon resonance (SPR) biosensor based on hollow gold nanospheres (HGNPs) and an improved sandwich assay was developed to detect rabbit IgG. The electromagnetic coupling between the HGNPs and Au film, and the notable plasmonic fields spread over the inner and outer surfaces of HGNPs, led to the considerable amplification of the SPR signal. Polydopamine-Ag@Fe3O4/reduced graphene oxide (PDA-Ag@Fe3O4/rGO) was introduced to bind detection antibody (Ab2) to form the improved sandwich structure. Ag nanoparticles were excited to produce SPR and their hot electrons were doped on graphene thin films, which amplified the response of biomolecules. Magnetic nanoparticles (Fe3O4) simplified the collection of Ab2-PDA-Ag@Fe3O4/rGO. An external layer of polydopamine (PDA) permitted the efficient immobilization of Ab2 without activation via abundant functional groups and protected the nanoparticles from etching or agglomeration. In addition, because of its large mass, Ab2-PDA-Ag@Fe3O4/rGO also played a key role in the further amplification of the SPR response signals. This novel SPR biosensor exhibited an effective response to the rabbit IgG at the different concentrations ranging from 0.019 to 40.00μgmL−1. This value is 132 times lower than that observed for a traditional SPR biosensor based on Au-3-mercaptopropionic acid and 8 times lower than that obtained from an Ab2 sandwich assay, which indicates that the SPR sensor has high sensitivity. In addition, the designed biosensor showed satisfactory recoveries to detect the rabbit IgG spiked in serum samples. Therefore, the novel SPR biosensor with high sensitivity and acceptable recovery has potential for practical applications.

Sensitivity enhancement of graphene coated surface plasmon resonance biosensor

In this paper, a highly sensitive surface plasmon resonance biosensor is presented using angular interrogation. Due to low sensitivity of conventional biosensor, graphene/two-dimensional transition metal are used in surface plasmon resonance biosensor to improve the sensitivity. Here, we propose a seven layer model of biosensor which shows by incorporating silicon layer in addition of transition metal dichalcogenides MoS2 and graphene, the sensitivity of the proposed SPR biosensor can be greatly enhanced than the conventional gold film SPR sensors. It is observed that the highest sensitivity can be obtained by optimizing the structure with 8 nm thickness of silicon layer, one layer of MoS2 and one layer of graphene. The highest sensitivity of our proposed sensor is 210°/RIU.

A highly sensitive surface plasmon resonance biosensor using photonic crystal fiber filled with gold nanowire encircled by silicon lining

The proposed photonic crystal fiber structure senses small deviations in the refractive index of liquids by surface plasmon resonance phenomenon. The coupling of core guided mode to surface plasmon polariton modes is modulated by the analyte placed between the central core and gold nanowire. Numerical study on the sensor performance is executed using finite element method. A sensitivity of 2000nm/RIU is achievable for detection of liquids with refractive index greater than 1.37 and the sensor covers a wide sensing range from 1.37 to 1.45. Loss factors as high as 187.76dB/cm is achievable. The analysis on the influence of structural modifications such as increase and decrease of gold nanowire diameter on the sensing action is also carried out. Numerical results depict an increase in confinement loss factor as the gold diameter gets reduced and a shift towards longer wavelength. The analysis of the sensor performance is performed when the gold nanowire is coated with silicon and it reveals that the loss factor gets enhanced by three fold, from 115.88 to 360.81dB/cm for analyte refractive index of 1.4, as compared to without silicon coating due to the enhanced energy coupling between plasmon and core modes. The increased silicon thickness improves the sensitivity factor to 4000nm/RIU.

High sensitivity surface plasmon resonance biosensor for detection of microRNA based on gold nanoparticles-decorated molybdenum sulfide

A high sensitive surface plasmon resonance (SPR) biosensor was proposed based on the gold nanoparticles-decorated molybdenum sulfide (AuNPs-MoS2) for the first time. This SPR platform using the AuNPs-MoS2 nanocomposites as signal labels for the sensitive and facile measurement of microRNA (miRNA) was executed in only two steps. At first, the thiol-modified DNA oligonucleotide probes, including a sequence complementary to the target miRNA-141, were fixed on the Au film to identify the segment sequence of target miRNA-141. Then, the assistant DNA-linked AuNPs-MoS2 nanocomposites were used to combine with the other section of the miRNA-141. Performance of SPR biosensor was enhanced by taking advantage of the AuNPs-MoS2 nanocomposites, thus this newly presented sensing assay exhibited high sensitivity toward miRNA with a detection limit of 0.5 fM. Furthermore, the method showed high specificity, resulting in distinguishing differences among miRNA-200 family members. Especially, the assay could also be used to detect human miRNA from cancer cells, and the results were in excellent accord with the ones obtained using qRT-PCR. What is more, this presented method could be feasible for determining miRNA in 10% human serum. This assay may provide a great potential as a miRNA quantification method in complex samples, and exert significant effect on biomedical research and clinical early diagnosis.

Highly sensitive surface plasmon resonance biosensor for the detection of HIV-related DNA based on dynamic and structural DNA nanodevices

Early detection, diagnosis and treatment of human immune deficiency virus (HIV) infection is the key to reduce acquired immunodeficiency syndrome (AIDS) mortality. In our research, an innovative surface plasmon resonance (SPR) biosensing strategy has been developed for highly sensitive detection of HIV-related DNA based on entropy-driven strand displacement reactions (ESDRs) and double-layer DNA tetrahedrons (DDTs). ESDRs as enzyme-free and label-free signal amplification circuit can be specifically triggered by target DNA, leading to the cyclic utilization of target DNA and the formation of plentiful double-stranded DNA (dsDNA) products. Subsequently, the dsDNA products bind to the immobilized hairpin capture probes and further combine with DDTs nanostructures. Due to the high efficiency of ESDRs and large molecular weight of DDTs, the SPR response signal was enhanced dramatically. The proposed SPR biosensor could detect target DNA sensitively and specifically in a linear range from 1pM to 150nM with a detection limit of 48fM. In addition, the whole detecting process can be accomplished in 60min with high accuracy and duplicability. In particular, the developed SPR biosensor was successfully used to analyze target DNA in complex biological sample, indicating that the developed strategy is promising for rapid and early clinical diagnosis of HIV infection.

High sensitivity surface plasmon resonance biosensor for detection of microRNA and small molecule based on graphene oxide-gold nanoparticles composites

A versatile and sensitive surface plasmon resonance (SPR) biosensor based on two layers of graphene oxide-gold nanoparticles (GO-AuNPs) composites was designed for the detection of microRNA (miRNA) and small molecule adenosine. The bottom layer, which acted as a functionalized substrate on the sensor chip, provided a high specific surface area convenient for the immobilization of capture DNA molecules. The upper layer served as a signal-amplification element. By employing these two layers of GO-AuNPs composites, the dual amplification strategy was achieved so that a measurement of miRNA-141 with a detection limit of 0.1fM was obtained. Moreover, the developed SPR biosensor showed decent selectivity toward miRNA-200 family members. Especially, the SPR biosensor demonstrated its applicability for the detection of miRNA-141 in cancer cell extractions, and the results obtained were consistent with those obtained by qRT-PCR. Interestingly, small molecule adenosine could also be detected using this SPR biosensor in combination with a split aptamer. Considering the superior sensitivity, selectivity and generality, this work promised much potential for the detection of various biomolecules.

Sensitivity Improved SPR Biosensor Based on the MoS2/Graphene–Aluminum Hybrid Structure

MoS2-graphene-based hybrid structures are biocompatible and useful in the field of biosensors. Herein, we propose a heterostructured MoS2/aluminum (Al) film/MoS2/graphene as a highly sensitive surface plasmon resonance (SPR) biosensor based on the Otto configuration. The sensitivity of the proposed biosensor is enhanced by using three methods. First, prisms of different refractive index have been discussed and it is found that sensitivity can be enhanced by using a low refractive index prism. Second, the influence of the thickness of the air layer on the sensitivity is analyzed and the optimal thickness of air is obtained. Finally, the sensitivity improvement and mechanism by using molybdenum disulfide (MoS2)–graphene hybrid structure is revealed. The maximum sensitivity ∼ 190.83°/RIU is obtained with six layers of MoS2 coating on both surfaces of Al thin film.

Ultrasensitive detection of endotoxins using computationally designed nanoMIPs

Novel molecularly imprinted polymer nanoparticles (nanoMIPs) were designed for endotoxin from Escherichia coli 0111:B4, using computational modeling. The screening process based on binding energy between endotoxin and each monomer was performed with 21 commonly used monomers, resulting in the selection of itaconic acid, methacrylic acid and acrylamide as functional monomers due to their strong binding interaction with the endotoxin template. The nanoMIPs were successfully synthesized with functional groups on the outer surface to aid in the immobilization onto sensor surface. The solid phase photopolymerization approach used for the synthesis of nanoMIPs ranging from 200 to 235 nm in diameter. The limit of detection and KD were significantly improved when endotoxin samples were prepared using a novel triethylamine method. This improved the efficiency of gold nanoparticle functionalization by targeting the subunits of the endotoxin. Compared to the vancomycin MIP control, the endotoxin MIPs displayed outstanding affinity and selectivity towards the endotoxin with KD values in the range of 4.4–5.3 × 10−10 M, with limits of detection of 0.44 ± 0.02 ng mL−1 as determined by surface plasmon resonance (SPR) sensor when itaconic acid was used as the functional monomer. The MIP surface can be regenerated >30 times without significant loss of binding activity making this approach highly cost effective for expensive analyte templates. The combination of molecular modeling and solid phase synthesis enabled the successful synthesis of nanoMIPs capable of recognition and ultrasensitive detection of endotoxins using the highly sensitive SPR biosensor with triethylamine method.

Graphene Coated High Sensitive Surface Plasmon Resonance Biosensor for Sensing DNA Hybridization

Graphene Coated High Sensitive Surface Plasmon Resonance Biosensor for Sensing DNA Hybridization

Graphene oxide–gold nanoparticles hybrids-based surface plasmon resonance for sensitive detection of microRNA

In this study, a simple and sensitive surface plasmon resonance (SPR) biosensor for miRNA detection was developed using graphene oxide–gold nanoparticles (GO–AuNPs) hybrids as signal amplification element. Taking advantage of the GO–AuNPs hybrids and their enhanced performance in SPR biosensors, the detection of miRNA was carried out in only two steps. Firstly, the thiolated capture DNA probe with a short complete complementary sequence was immobilized on the Au film surface to recognize the part sequence of target miRNA. Subsequently, the assistant DNA-linked GO–AuNPs hybrids were employed to bind the other section of the target. It was found that the developed SPR biosensor was able to achieve a detection limit as low as 1fM. Moreover, the method showed excellent ability to discriminate differences among miRNA-200 family members. Notably, human miRNA from cancer cells could also be detected, and the results were in excellent agreement with the ones obtained using qRT-PCR. On the basis of these findings, we believe that this method has great potential for quantitative detection of miRNA in biomedical research and early clinical diagnostics.

Improved screening of microcystin genes and toxins in blue-green algal dietary supplements with PCR and a surface plasmon resonance biosensor

Microcystins (MCs) comprise a group of cyclic heptapeptide toxins that share a common backbone and have two variable l-amino acids that yield at least 21 known analogs of varying potency. These hepatotoxins and potential tumor promoters are produced by certain cyanobacteria, including Microcystis aeruginosa. The cyanobacterium M. aeruginosa blooms in freshwater lakes and can potentially co-occur with other species such as Aphanizomenon flos-aquae, which is targeted and harvested for the production of dietary supplements known as blue-green algae (BGA). BGA supplements are currently marketed in the U.S. and internationally as a product that may elevate mood, increase energy, and alleviate attention deficit hyperactivity disorder. However, the potential for BGA dietary supplements to be contaminated with MCs is of concern, and there are currently no validated methods for detection of MCs in these products. This research focused on establishing screening methods for toxic Microcystis and MCs in BGA supplements. A DNA-based method employing polymerase chain reaction (PCR) was used as a prescreening tool to evaluate the dietary supplements and to detect the presence of toxin genes (i.e., presence of toxic Microcystis). A rapid, sensitive surface plasmon resonance (SPR) biosensor, directed towards recognition of all MC forms, was also developed and validated. This improved SPR biosensor incorporates a commercial Adda-group antibody (Ab) that has the capacity for broader recognition of MCs than previously developed sensors for BGA supplements that rely solely on an arginine-reactive Ab and can quantitate MC levels down to 0.24ng/mL (equivalent to 0.24μg per gram of BGA supplement) in less than 10min. Such a rapid, quantitative screening method may allow for further surveillance of BGA products to assist risk assessment efforts, establishment of regulatory guidance levels, and response to potential consumer complaints related to BGA products. The PCR technique and SPR biosensor may be used in concert as prescreening and screening tools, respectively or individually, thereby limiting the number of samples that must be evaluated with confirmatory methods.

Investigation of phase SPR biosensor for efficient targeted drug screening with high sensitivity and stability

We investigate an application case study of a phase sensitive surface plasmon resonance (SPR) biosensor based on Mach–Zehnder configuration for efficient targeted drug screening, where calculating reaction kinetic constants, inhibition effect and cytotoxicity analysis are three key factors in the evaluation. As a typical targeted drug, cetuximab is selected in the measurements assisted by the phase SPR biosensor with a sensitivity of 10−6 in terms of refractive index unit (RIU) and stability of 6×10−7RIU in 80min. The reaction kinetic constants of cetuximab binding to epidermal growth factor receptor (EGFR) are found as: kd (dissociation constant)=1.75±0.29×10−3S−1, kD (equilibrium dissociation constant)=4.19±0.58nM. The results of inhibition effect analysis show that cetuximab can block EGFR binding to its two ligands, epidermal growth factor (EGF) and EGFR-transforming growth factor α (TGF-α). This effect has been tested in three cell lines of lung adenocarcinoma, colon cancer and breast cancer. Comparing to other conventional methods, we find that the phase SPR biosensor can determine the cell sensitivity to cetuximab in just 4h. As a label-free, real-time, high sensitivity and stability biosensor, the phase SPR biosensor is a potential optical technique for targeted drug screening and analysis of cell resistance to drugs with comparative advantages.

Studies of gold nanorod-iron oxide nanohybrids for immunoassay based on SPR biosensor

A wavelength modulation surface plasmon resonance (SPR) biosensor based on gold nanorods-Fe3O4 (GNR-Fe3O4) nanohybrids was developed for the determination of mouse IgG. The premade negatively charged Fe3O4 nanoparticles were coated on the surface of positively charged GNRs through electrostatic interaction. The synthetic method was simple, quick and easy operation. The aldehyde group functionalized GNR-Fe3O4 nanohybrids possess unique magnetic property, exceptional optical property and good biocompatibility, which can be used as immobilization matrix for biomolecules. The magnetic nanohybrids can be easily immobilized on the surface of SPR biosensor chip with a magnetic pillar, which simplifies the experimental procedure. The effects of GNR-Fe3O4 nanohybrids on the sensitivity of SPR biosensor were also studied. The SPR biosensor based on GNR-Fe3O4 nanohybrids shows a good response to mouse IgG in the concentration range of 0.15–40.00μgmL−1, while the biosensor based on MPA and Fe3O4 nanoparticles show a good response to mouse IgG in the concentration range of 2.50–40.00μgmL−1 and 1.25–40.00μgmL−1, respectively. As a result, when GNR-Fe3O4 nanohybrids were used in SPR biosensor, the sensitivity for the determination of mouse IgG is significantly enhanced.

근접장-분자반응 간의 중첩을 이용한 표면 플라스몬 공명 센서 감도 평가에 관한 연구

In this study, we have investigated the correlation of far-field detection sensitivity of surface plasmon resonance (SPR) biosensors with optical signatures associated with the near-field overlap of biomolecules. The results confirm a direct relation between the far-field and near-field parameters, particularly for optical signatures defined in terms of lateral electric field components that are tangential to the interface and thus continuous across the interface. The overall correlation between near-field optical signatures and far-field resonance shift exceeded 97%. The results can be highly useful to evaluate detection sensitivity of SPR biosensors that take advantage of complex structures for localization of surface waves.

Preparation and application of triangular silver nanoplates/chitosan composite in surface plasmon resonance biosensing

This paper reports the utilization of triangular silver nanoplates (TSNPs) to enhance the sensitivity of surface plasmon resonance (SPR) biosensor. TSNPs modified with 3-mercaptopropinic acid (MPA) were simply mixed with chitosan and glutaraldehyde to form TSNPs/chitosan composite. The composite was deposited on Au film as immobilization substrate for SPR biosensor. The novel structures of TSNPs are preserved against etching by MPA and chitosan polymer. Moreover, chitosan cross-linked by glutaraldehyde enables antibody to be immobilized on fabricated substrate directly via Schiff alkali reaction. In the optimized conditions, the resulting biosensor based on TSNPs/chitosan composite shows a satisfactory response to bovine IgG in the concentration range of 0.075–40.00μgmL−1. While the biosensor based on chitosan without TSNPs shows a response in the concentration range of 0.6–40μgmL−1 and the biosensor based on Au film shows a response in the concentration range of 2.5–40μgmL−1. The experiment results show that the sensitivity of SPR biosensor based on TSNPs/chitosan composite was significantly enhanced and the immobilization procedure of antibody was simplified.

Studies of Fe3O4/Ag/Au composites for immunoassay based on surface plasmon resonance biosensor

A novel method immunosensor based on chemically functionalized Fe3O4/Ag/Au nanocomposite was developed. Fe3O4/Ag seeds were coated with Au and Fe3O4/Ag/Au nanocomposites were obtained. The nanocomposites could be obtained without violent stirring and the operation was easy and convenient. The magnetic nanocomposites can be easily immobilized on Au film of the surface plasmon resonance (SPR) biosensor with a magnetic pillar. The immobilization of Fe3O4/Ag/Au nanocomposites on the Au film leads to a large shift in resonance wavelength, which is due to the increase of the sensing membrane thickness, high dielectric constant of Ag and Au particles, and electromagnetic coupling between Fe3O4/Ag/Au nanocomposites and the Au film. The effects of Fe3O4/Ag/Au nanocomposites on the sensitivity of SPR biosensor were also investigated. As a result, the biosensor based on Au film shows a response for dog IgG in the concentration range of 1.25–20.00μgml−1, whereas the SPR biosensor based on Fe3O4/Ag/Au nanocomposites shows a response for dog IgG in the concentration range of 0.15–40.00μgml−1. The sensitivity of the SPR biosensor based on Fe3O4/Ag/Au nanocomposites is higher than that based on Au film.

An experimental correlation study between field–target overlap and sensitivity of surface plasmon resonance biosensors based on sandwiched immunoassays

In this report, we have studied the effectiveness of field–target overlap to evaluate detection sensitivity of surface plasmon resonance (SPR) biosensors. The investigation used theoretical analysis based on the transfer matrix method, which was experimentally confirmed by thin film-based detection in sandwich and reverse sandwich immunoglobulin G (IgG) assays. Both theoretical and experimental results show that strong correlation exists between the overlap and the sensitivity with the coefficient of correlation higher than 95% in all the cases that we have considered. We have also confirmed the correlation in diffraction grating-based SPR measurement of IgG/anti-IgG interactions. The correlation elucidates the mechanism behind the far-field detection sensitivity of SPR biosensors and can lead to the enhancement of SPR biosensing with molecular scale sensitivity.

Surface plasmon resonance biosensor based on Fe 3O 4/Au nanocomposites

In this paper, the core/shell Fe 3O 4/Au nanocomposites modified with 3-mercaptopropionic acid (MPA) were prepared and applied in the surface plasmon resonance (SPR) biosensor. And the detailed investigation of Fe 3O 4/Au nanocomposites was separately performed by UV–vis spectroscopy and transmission electronic microscopy. As the magnetic property and exceptional optical properties, the Fe 3O 4/Au nanocomposites were used as the solid support for the goat anti-human IgM, which could be immobilized on the surface of SPR biosensor chip by a magnetic pillar. This novel method of immobilizing goat anti-human IgM simplified experimental procedures and facilitated the regeneration of the sensing membrane. In addition, the different diameter of Fe 3O 4/Au nanocomposites could be obtained with the different amount of MPA in the solution. And the effect of Fe 3O 4/Au nanocomposites with different diameters on the sensitivity of SPR biosensor was also explored. As a result, the SPR biosensor exhibits a satisfactory response for human IgM in the concentration range of 0.30–20.00 μg ml −1 and the increasing nanocomposite diameter is in favor of the sensitivity enhancement of SPR biosensor.

Sensitivity-enhancement of wavelength-modulation surface plasmon resonance biosensor for human complement factor 4

Sandwich and colloidal Au techniques for enhancing the sensitivity of a wavelength-modulation surface plasmon resonance (SPR) immunosensor are demonstrated by the detection of human complement factor 4 (C4). The design of the wavelength-modulation SPR biosensor is based on fixing the incident angle of light and measuring the reflected intensity of light in the wavelength range spanning 500–900 nm simultaneously. The human C4 had good response in the concentration range 2–20 μg/mL in the direct assay. However, in the sandwich assay, the human C4 had good response in the concentration range 0.2–20 μg/mL and the lowest concentration is 10-fold lower than that obtained by the direct assay. With human C4-Au colloidal conjugate, the human C4 had good response in the concentration range 0.1–20 μg/mL and the lowest concentration is 20-fold lower than that obtained by the direct assay. In the colloidal-Au-enhanced sandwich assay, the human C4 had good response in the concentration range 0.05–5 μg/mL and the lowest concentration is 40-fold lower than that obtained by the direct assay. Under selected experimental conditions, the reproducibility, sensitivity, and reversibility of the enhanced SPR immunoassay are very satisfactory. The results represent potentially significant advantages in the sensitivity of SPR biosensors.

P1/P1′ modified HIV protease inhibitors as tools in two new sensitive surface plasmon resonance biosensor screening assays

The commonly used HIV-1 protease assays rely on measurements of the effect of inhibitions on the hydrolysis rate of synthetic peptides. Recently an assay based on surface plasmon resonance (SPR) was introduced. We have taken advantage of the fact that the SPR signal is proportional to the mass of the analyte interacting with the immobilised molecule and developed two new improved efficient competition assay methods. Thus, high molecular weight binders were used as amplifiers of the surface plasmon resonance signal. Linkers were attached by a Heck reaction to the para-positions of the P1/P1′ benzyloxy groups of a linear C 2-symmetric C-terminal duplicated inhibitor to enable (a) biotin labelling or (b) direct immobilisation of the inhibitor to the biosensor surface matrix. The interaction properties of a series of 17 structurally diverse inhibitors was assessed and compared to previously reported data. The most sensitive assay was obtained by immobilising the enzyme and amplifying the signal with an antibody, giving a detection range between 0.1 nM and 10 μM. Immobilisation of the inhibitor resulted in a stable and durable surface but a narrower detection range (1–100 nM). The two competition assays are anticipated to be very suitable for fast screening of potential HIV inhibitors.