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Plasmonic sensors are ideally suited for the design of small, integrated, and portable devices that can be employed in situ for the detection of analytes relevant to environmental sciences, clinical diagnostics, infectious diseases, food, and industrial applications. To successfully deploy plasmonic sensors, scaled-down analytical devices based on surface plasmon resonance (SPR) and localized surface plasmon resonance (LSPR) must integrate optics, plasmonic materials, surface chemistry, fluidics, detectors and data processing in a functional instrument with a small footprint. The field has significantly progressed from the implementation of the various components in specifically designed prism-based instruments to the use of nanomaterials, optical fibers and smartphones to yield increasingly portable devices, which have been shown for a number of applications in the laboratory and deployed on site for environmental, biomedical/clinical, and food applications. A roadmap to deploy plasmonic sensors is provided by reviewing the current successes and by laying out the directions the field is currently taking to increase the use of field-deployed plasmonic sensors at the point-of-care, in the environment and in industries. [ABSTRACT FROM AUTHOR]

A term project was introduced in teaching advanced spectroscopy and notions of nanotechnology to chemistry students at the graduate level (M.Sc. and Ph.D.). This project could also be suited for an honor's thesis at the undergraduate level. Students were assigned a unique combination of nanoparticle synthesis (13 nm Au nanospheres, ~100 nm nanoraspberries or ~50 nm nanostars) and fluorescent/Raman-active ligand (HS-PEG-FITC, rhodamine 6G, 4-mercaptobenzoic acid, 4-nitrobenzenethiol, and phenanthroline). Characterization with transmission electron microscopy allowed the students to confirm the shape and size distribution of nanoparticles. The ligands immobilized on the surface of the nanoparticles were extensively characterized using a suite of optical techniques. UV-vis was used to observe the plasmonic bands of particles of varying shapes, and fluorescent spectroscopy was used to construct fluorescent pathways with the aid of Jablonski diagrams. The vibrational bands of the ligands were identified using IR and Raman spectroscopy. Performing surface-enhanced Raman spectroscopy (SERS) on the nanoparticle at different excitation wavelength (488, 633, and 785 nm) was used to understand the influence of the surface plasmon on SERS and fluorescence spectroscopies. Students were required to write a full scientific paper for the report of the term project. [ABSTRACT FROM AUTHOR]

Integrating a SERS immunoassay on a plasmonic "patch clamp" nanopipette enabled nanobiosensing for the detection of IgG. A SERS response was obtained using a sandwich assay benefiting from plasmon coupling between a capture Au nanoparticle (AuNP) on a nanotip and a second AuNP modified with a Raman active reporter and an antibody selective for IgG. The impact of nanoparticle shape and surface coverage was investigated alongside the choice of Raman active reporter, deposition pH, and plasmonic coupling, in an attempt to fully understand the plasmonic properties of nanopipettes and to optimize the nanobiosensor for the detection of IgG. These probes will find applications in various fields due to their nanoscale size leading to the possibility of spatially and temporally addressing their location near cells to monitor secretion of biomolecules. [ABSTRACT FROM AUTHOR]

Surface plasmon resonance (SPR) biosensing has matured into a valuable analytical technique for measurements related to biomolecules, environmental contaminants, and the food industry. Contemporary SPR instruments are mainly suitable for laboratory-based measurements. However, several point-of-measurement applications would benefit from simple, small, portable and inexpensive sensors to assess the health condition of a patient, potential environmental contamination, or food safety issues. This Trend article explores nanostructured substrates for improving the sensitivity of classical SPR instruments and nanoparticle (NP)-based colorimetric substrates that may provide a solution to the development of point-of-measurement SPR techniques. Novel nanomaterials and methodology capable of enhancing the sensitivity of classical SPR sensors are destined to improve the limits of detection of miniature SPR instruments to the level required for most applications. In a different approach, paper or substrate-based SPR assays based on NPs, are a highly promising topic of research that may facilitate the widespread use of a novel class of miniature and portable SPR instruments. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Nanomaterials developed for localized surface plasmon resonance (LSPR) are increasingly integrated to classical prism-based SPR sensors, providing enhanced sensitivity and lower detection limits. The unique properties of these novel nanomaterials in addition to novel surface chemistry to minimize nonspecific adsorption and surface plasmon-coupled techniques with other spectroscopic or mass spectrometry techniques are highlighted in this article. [ABSTRACT FROM AUTHOR]

The physiological application of amperometric adenosine triphosphate (ATP) microbiosensors for characterizing the stimulus-response at rat carotid bodies superfused with high potassium concentrations, during normoxic hyper-capnia, and during hypoxia is demonstrated using the peripheral arterial chemoreceptors in the carotid body of rats as a model system. Amperometric microbiosensors based on glucose oxidase (GOD) and hexokinase (HEX) immobilized within a polymer matrix at the surface of Pt disk microelectrodes (diameter: 25 μm) are positioned at a distance of approximately 100 μm above the carotid body surface for detecting extracellular ATP. A linear calibration function of ATP microbiosensors in the physiologically relevant concentration range of 0-40 μM ATP enables quantitative detection of ATP released at the carotid body surface in response to physiological stimuli. It is shown that these stimuli induce extracellular ATP release from the carotid body at levels of 4-10 μM. Other electroactive neurotransmitters such as, e.g., catecholamines are coreleased by the carotid body at hypercapnic, hypoxic and high-potassium stimulus, are simultaneously detected utilizing a dual-electrode assembly with an ATP microbiosensor and a second bare channel providing a colocalized reference measurement for ATP quantification. [ABSTRACT FROM AUTHOR]

HEPES-based biological buffer is subject to photooxidation upon exposure to fluorescent illumination. Thereby hydrogen peroxide is generated, which interferes with amperometric oxidoreductase-based biosensors for glucose or adenosine triphosphate (ATP). These biosensors operate at an oxidation potential above 500 mV vs. the standard calomel electrode (SCE) and involve hydrogen peroxide as the electroactive molecule detected at the electrode surface. False-positive detection of ATP was observed in HEPES buffer utilizing an amperometric microbiosensor based on the co-immobilization of glucose oxidase and hexokinase for detection of ATP in biological specimens. Electrochemical, mass spectrometric, 31P NMR, and 1H NMR studies indicate that complexation of ATP and HEPES induced by the presence of Ca2+ in HEPES buffer decreases the photooxidation of HEPES. Consequently, the hydrogen peroxide background concentration is reduced, thereby leading to erroneous ATP detection at the dual-enzyme microbiosensor, which determines an increase in ATP via a reduced hydrogen peroxide signal. [ABSTRACT FROM AUTHOR]

A general theoretical model for competitive dual-enzyme microbiosensors based on self-assembled monolayers (SAM) is presented. The model is derived for amperometric dual-enzyme ATP sensors and provides excellent agreement with experimental ATP measurements at 25 μm diameter microelectrodes. In this model, the statistical probability of a glucose molecule in competition between two enzymes, glucose oxidase (GOD)/hexokinase (HEX), at the ATP sensor surface is combined with the enzymatic reaction rate. Thereby, a simple model predicting the sensor signal for varying surface concentrations of GOD and HEX, glucose concentration, and ATP concentration is obtained. Excellent agreement of the predicted current signal with experimentally obtained sensor signals was achieved at ATP concentrations between 10 and 300 μM in a buffer containing glucose at physiologically relevant levels. Consequently, the development time for new dual-enzyme biosensors can be reduced, and an analytical model for the sensor response function is provided facilitating the calibration of enzymatic biosensors. [ABSTRACT FROM AUTHOR]

Abstract: Covalent attachment of glucose oxidase to a pre-activated 16-mercaptohexadecanoic acid at a gold ultramicroelectrode surface improves sensitivity, stability, and reproducibility of enzyme-based amperometric microbiosensors. Self-assembled monolayers of the N-hydroxysuccinimide ester of 16-mercaptohexandecanoic acid (NHS-MHA) at gold electrodes enable spontaneous covalent linking of glucose oxidase to the gold surface of ultramicroelectrodes. By self-assembling NHS-MHA for 30min, approximately 93% of the electrode surface is covered, thereby maximizing both the number of attachment sites for glucose oxidase, and sufficient diffusion of hydrogen peroxide to the gold electrode. The glucose oxidase reaction with NHS-MHA was optimized at pH of 6.5, and at a temperature of 43°C, resulting in a surface concentration of 6.8±0.6×1011 enzymemoleculescm−2. Thus obtained amperometric microbiosensors were calibrated in the range of 1–10mM providing excellent correlation with the theoretical prediction of the microbiosensor response. The reported sensitivity of these microbiosensors documents an improvement by one order of magnitude compared to other approaches for covalent enzyme attachment. This is attributed to the NHS-MHA layer spacing the enzymatic recognition interface further from the electrode surface, thereby minimizing quenching of the enzyme activity. [Copyright &y& Elsevier]

Two mycocardial infarction biomarkers, myoglobin (MG) and cardiac troponin I (cTnI), were quantified at biological levels and in undiluted serum without sample pretreatment using surface plasmon resonance (SPR) sensors. To achieve detection of biomarkers in undiluted serum (72 mg/mL total protein concentration), minimization of the nonspecific signal from the serum protein was achieved by immobilizing the antibody for the biomarkers on an N-hydroxysuccinimide activated 16-mercaptohexadecanoic acid self-assembled monolayer. This monolayer reduces the nonspecific signal from serum proteins in such a manner that short exposure of the sensor to serum prior to analysis prevents any further nonspecific adsorption during analysis. Thus, sensing of MG and cTnI was achieved on the basis of the difference between signals from the active sensor and a reference sensor that captured background interference. This resulted in direct measurement of these biomarkers in undiluted serum. Detection limits for both markers were below 1 ng/mL, which is below the threshold needed to detect myocardial infarction. Detecting biomarkers in the low ng/mL range without signal amplification in such a complex matrix as serum corresponds to a selectivity of 108. The root-mean-square-error (RMSE) of calibration was below 2 ng/mL. [ABSTRACT FROM AUTHOR]

Reduction of the nonspecific serum protein adsorption on a gold surface to levels low enough to allow the detection of biomarkers in complex media has been achieved using the N-hydroxysuccinimide (NHS) ester of 16-mercaptohexadecanoic acid. Carboxymethylated dextran (CM dextran), which is widely used, nonspecifically adsorbs enough proteins to mask the signal from target biomarkers in complex solutions such as serum or blood. The use of short-chain thiols greatly reduces the amount of nonspecific protein adsorption. Mixed layers of 11-mercaptoundecanoic acid or the NHS ester of 11-mercaptoundecanoic acid mixed layers with either 11-mercaptoundecanol or undecanethiol, and 16-mercaptohexadecanoic acid or the NHS ester of 16-mercaptohexadecanoic acid with hexadecanethiol, were also investigated for nonspecific protein binding properties as well as for biomarker signal response. The NHS ester of 16-mercaptohexadecanoic acid exhibits the largest signal for the biomarker myoglobin (including CM dextran) while offering a significantly diminished amount of nonspecific binding. The sensor has also been shown to detect interleukin-6 in cell culture media containing protein concentrations of at least 4 mg/mL. [ABSTRACT FROM AUTHOR]

Bitumen is a complex mixture of hydrocarbons for which microstructural knowledge is incomplete. In an effort to detail this microstructure, 13 bitumens were analysed by phase-detection atomic force microscopy. Based on morphology, the bitumens could be classified into three distinct groups. One group showed fine domains down to 0.1 µm, another showed domains of about 1 µm, and a third group showed up to four different domains or phases of different sizes and shapes. No correlation was found between the atomic force microscopy morphology and the composition based on asphaltenes, polar aromatics, naphthene aromatics and saturates. A high correlation was found between the area of the ‘bee-like’ structures and the vanadium and nickel content in bitumen, and between the atomic force microscopy groups and the average size of molecular planes made of fused aromatics. The morphology and the molecular arrangements in bitumen thus appear to be partly governed by the molecular planes and the polarity defined by metallic cations. [ABSTRACT FROM AUTHOR]

Sensing of three cytokines related to chronic wound healing, interleukin-1 (IL-i), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), with detection limits at or below 1 ng/mL in buffered saline solution and spiked cell culture medium (CCM) has been achieved. Fiber-optic surface plasmon resonance (SPR) sensors are coated with an antibody binding layer and antibodies specific to the cytokine of interest are covalently attached to this layer. To achieve such detection limits in a complex medium such as CCM, total protein content of 4 mg/mL, the use of a novel N-hydroxysuccinimide ester of 16-mercapto-hexadecanoic acid (NHS-MHA) is necessary. A comparison of the detection limits for IL 6 using currently widely used CM-dextran and NHS-MHA shows an improvement by a factor of 3 using NHS-MHA. The detection limits for the monitoring of cytokines in spiked saline solutions and CCM were similar for TNF-α and slightly higher for IL-1 and IL-6. The detection of each cytokine in the presence of interfering agents resulted in concentration prediction well within the error of calibration. The SPR sensors are stable in CCM after 20 mm of pretreatment in CCM, minimizing the reliance on a reference sensor to quantify the cytokines in complex media. This technique enables a major advancement in the field of real-time monitoring of biologically relevant molecules in complex biological fluids. [ABSTRACT FROM AUTHOR]

Abstract: Single-crystal sapphire-fiber optic sensors based on surface plasmon resonance (SPR) for refractive index (RI) measurements of aqueous and hydrothermal water solutions are described. Accurate measurement of RIs is essential to efficient operation and control of broad range of engineering processes. Some of these processes are carried out with harsh environments, such as high-temperature, high pressure, and chemical corrosion. These extreme physical conditions are proving a limiting factor in application of the conventional silica-based optical sensors. Single-crystal sapphire is an ideal material for sensor applications, where reliable performance is required in the extreme environment conditions. With regard to the liquid species detection, most applications of SPR sensors are designed to function near the refractive index of water (1.3330RI). The RI changes of aqueous solution can be easily monitored by silica-fiber (RI, 1.4601 at 550nm) based SPR sensor. However, the sapphire waveguide has a prohibitively high RI (1.7708 at 546nm) for unmodified monitoring of the RI changes of aqueous solutions. For that purpose, a practical SPR probe geometry has been applied to the ability to tune the SPR coupling wavelength/angle pair with sapphire-fiber based SPR probe. [Copyright &y& Elsevier]

Abstract: The elimination or minimization of non-specific protein adsorption from serum is critical for the use of surface plasmon resonance (SPR) sensors for in vitro and in vivo analysis of complex biological solutions. The ultimate goals in this application are to minimize non-specific adsorption of protein and to maximize analyte signal. A reduction of the non-specific protein adsorption from serum of up to 73% compared to carboxymethylated-dextran 500kDa (CM-dextran) was achieved following a survey of eight biocompatible polymers and 10 molecular weights of CM-dextran. These coatings minimize non-specific adsorption on the sensor while also serving as immobilization matrices for antibody fixation to the probes. Polymers including polysaccharides: CM-dextrans, CM-hyaluronic acid, hyaluronic acid, and alginic acid were investigated. Humic acid, polylactic acid, polyacrylic acid, orthopyridyldisuldfide–polyethyleneglycol–N-hydroxysuccinimide (OPSS–PEG–NHS), and a synthesized polymer; polymethacrylic-acid-co-vinyl-acetate (PMAVA) were also used. The non-specific protein adsorption reduction was measured over a 14 day period at 0°C for each polymer. Calibration curves using some of these polymers were constructed to show the performance and low detection limit possibilities of these new antibody supports. For many of the polymers, this is the first demonstration of employment as an antibody support for an optical or surface active sensor. CM-dextran is the polymer offering the largest signal for the antigen detection. However, the biocompatible polymers demonstrate a greater stability to non-specific binding in serum. These biocompatible polymers offer different alternatives for CM-dextran. [Copyright &y& Elsevier]

Abstract: The analysis of the excess dielectric properties for various binary mixtures and a ternary mixture is demonstrated using a surface plasmon resonance (SPR) sensor. Strong deviations from ideality are seen using SPR to monitor deviations in the dielectric properties following mixing. Binary mixtures with similar refractive index were measured: hexanes/isopropanol, n-heptanes/propanol, 1-acetoxy-2-methoxyethane/2-methoxyethanol, butanol/dipropylamine, hexanes/ethylacetate, and ethylacetate/isopropanol binary mixtures. The ternary mixture was composed of 60 different proportions of hexanes, isopropanol, and ethylacetate. Using SPR, mixing dynamics is easily accessible. The mixing of hexanes and isopropanol in static solution was monitored. [Copyright &y& Elsevier]

Abstract: The preparation of a novel carboxymethylated dextran photochromic polymer on a gold surface is presented here. Ethylester-dihydroindolizine is attached by amine coupling to a carboxymethylated dextran polymer on the gold surface of a Surface Plasmon Resonance (SPR) sensor. The photoinduced switch between the two isomers of the ethylester-dihydroindolizine photochromic polymer was investigated by fiber optics based surface plasmon resonance. The different solvent effect on the SPR shift is also reported. A larger absolute shift was obtained in solvents with low relative dielectric constants, than in solvents with a larger relative dielectric constant. A blue shift was observed with organic solvents and a red shift for the aqueous solvent. Moreover, by changing the solvent, the refractive index of the surrounding media in contact with the gold surface also changes and the wavelength used to excite the surface plasmon can be shifted outside the excitation/relaxation range of the photochromic system. [Copyright &y& Elsevier]

The preparation and use of multiple polymers attached to a surface plasmon resonance (SPR) sensor for optimization of signal enhancement and minimization of fouling during sensing of biological species has been achieved. These polymers are advantageous compared to the current practice of carboxymethylated-dextran (CM-dextran). The polymers offer a wide range of functionalities and different molecular weights. Using these polymers, the SPR sensors can be fabricated as fast or faster than the CM-dextran sensor. In this study, we investigated the use of nine polymers for SPR biosensors. Polysaccharides, including CM-dextran, CM-hyaluronic acid, hyaluronic acid, and alginic acid, were investigated. Humic acid, polylactic acid, polyacrylic acid, orthopyridyldisulfide-polyethyleneglycol-N-hydroxysuccinimide (OPSS-PEG-NHS) and a synthesized polymer; polymethacrylic-acid-co-vinyl-acetate (PMAVA), were also used. The polymers were chemically attached to a thiol monolayer on the SPR biosensor using carbodiimide chemistry. The polymers were functionalized for binding of anti-myoglobin (anti-MG). The sensor performance was measured using myoglobin (MG) at 25 ng ml-1, a biologically relevant level for myocardial infarction detection. Most polymers offered similar performance to CM-dextran for MG detection in HEPES buffer saline pH 7.4 (HBS). In preliminary studies in bovine serum, each of the candidate polymers demonstrated better performance than CM-dextran. [Copyright &y& Elsevier]

A series of thermally shrinkable polymer surface-enhanced Raman scattering (SERS) substrates were prepared with bimetallic Au and Ag (oxidized or not) films and with Au nanoparticles (AuNPs) located at different places in the layered structure to evaluate the synergistic effect of different known SERS amplification methods to enhance the Raman signal for low concentration dopamine detection. A bimetallic Au and Ag layered structure improved the Raman signal by 5 and 2 times compared to the single-layered Au and Ag films. Oxidizing the Ag layer prior to deposition of Au further improved the signal by a factor of 2, while adding AuNP on wrinkled films increased another 10 times the intensity of the Raman signal. It was found that the enhancement was another 10 times stronger when using AuNPs in combination with other means of enhancement such as with a silver underlayer or surface wrinkling. Wrinkling alone only gave a few-fold increase compared to a flat film, but the combination of wrinkling with AuNPs and a silver underlayer improved the SERS intensity by more than 3 orders of magnitude, showing the synergistic effect of these enhancement methods. The optimized sensors were then tested in dynamic SERS with low concentration dopamine solutions, where the signal showed characteristics of a digital SERS response. Raman spectra preprocessing and sorting software was developed to triage the SERS-active spectra from the null spectra, to count the detection events such as the ones observed in single molecule experiments. [ABSTRACT FROM AUTHOR]

Bovine serum albumin (BSA) containing buffers are the standard blocking buffer in biosensing, yet human serum is the intended application for most clinical sensors. However, the effect of human serum albumin (HSA) on binding assays remains underexplored. A simple and well-studied assay (human IgG/goat anti-human IgG) was investigated with a surface plasmon resonance (SPR) sensor to address this fundamental question in sensing. Calibrations were performed with buffers containing various concentrations of bovine or human serum albumin, as well as full and diluted bovine or IgG-depleted human serum. It was found that HSA or human serum, but not BSA or bovine serum, significantly affected the SPR shift and binding constants of the assay. Interestingly, large differences were also observed depending on whether the animal or human antibody was immobilized on the SPR chip for detection, highlighting that matrix protein/analyte/receptor interactions play a significant role in the response. We find that the interaction of soluble HSA with human IgG interferes with the recognition region, affecting the binding constant, and thus results obtained in BSA are not necessarily applicable to clinical samples or in vivo conditions. We also clearly demonstrate why a minimum dilution of 1 : 10 is often required in SPR assays to remove most background effects. Taken together, these results show that: (1) BSA does not affect the binding constant between antibodies and thus serves its purpose well when only surface blocking is intended, (2) HSA is an adequate surrogate for human serum in assay optimization, and (3) blocking buffers should be prepared with HSA in the optimization steps of assays to be translated to human blood or serum. [ABSTRACT FROM AUTHOR]

Driven by the urgent need for recognition and quantification of trace amino acids enantiomers in various biologic samples, we demonstrate for the first time an ultrasensitive electrochemical chiral biosensor for cysteine (Cys) based on magnetic nanoparticles (Fe3O4@PDA/CuxO) as electrode units. D-Cys-Cu2+-D-Cys formed in the presence of cysteine exhibits strong stability and a shielding effect on the redox current of indicator Cu2+, which can be used to quantify and recognize D-Cys by square wave voltammetry. Simultaneous detection of D-Cys and homocysteine (Hcy) is achieved in the presence of other amino acids, demonstrating an excellent selectivity of the sensor. Moreover, aided by the enrichment treatment effect of magnetic micronanoelectrodes, an ultrahigh sensitivity up to 102 μA μM-1 cm-2 was achieved, the detection limit is reduced to picomolar level (83 pM) for DCys and can be used for the recognition of cysteine enantiomers. The proposed method has been verified by real sample analysis with satisfactory results. The results highlight the feasibility of our proposed strategy for magnetic micronanoelectrode sensor, electrochemical recognition, and quantification of D-Cys, which can be more broadly applicable than that with traditional electrode structures and further advance the field of electrochemical sensors. [ABSTRACT FROM AUTHOR]

ATP mediates chemoexcitation via binding to P2X2-P2X3 receptors. We developed amperometric ATP microbiosensors to determine the role of ATP in mediating maturation of chemosensitivity of peripheral arterial chemoreceptors at the carotid body (CB) to physiological stimuli. ATP is detected by immobilizing glucose oxidase and hexokinase within a polymer matrix at the surface of a 25 µm-diameter Pt disk electrode. The age-dependent ATP release from CBs was measured in real-time in response to hypoxia ([O2] < 1 ppm), and to normoxic hypercapnia (10-12% CO2). During hypoxia, ATP released at the CB was 4.3 ± 0.3 µM (median = 4.2 µM, n = 9) in rats between 3-6 postnatal days (PNDs), which increased to 91 ± 28 µM ATP (median = 19 µM, n = 6) at CBs of rats between 16-20 PNDs. The significant difference in ATP release from CBs of older animals suggests that hypoxic ATP release mechanisms are maturating during the 3rd week of postnatal development. However, in response to hypercapnia ATP release was only 6.1 ± 0.9 µM (median = 4.9 µM, n = 7) during the 3rd week, indicating that the development of hypercapnic ATP release mechanisms is different from hypoxia in rats. The 5-fold increase in ATP release in response to hypoxia during the first 3 weeks of postnatal development may contribute to the increase in hypoxic chemosensitivity, which occurs during early postnatal development. [ABSTRACT FROM AUTHOR]

Therapeutic drug monitoring (TDM) is required for pharmaceutical drugs with dosage limitations or toxicity issues where patients undergoing treatment with these drugs require frequent monitoring. This allows for the concentration of such pharmaceutical drugs in a patient's biofluid to be closely monitored in order to assess the pharmacokinetics, which could result in an adjustment of dosage or in medical intervention if the situation becomes urgent. Biosensors are a class of analytical techniques competent in the rapid quantification of therapeutic drugs and recent developments in instrumental platforms and in sensing schemes, as well as the emergence of nanobiosensors, have greatly contributed to the principal examples of these sensors for therapeutic drug monitoring. Based on initial success stories, it is clear that (nano)biosensors could pave the way for therapeutic drug monitoring of many commonly administered drugs and for new drugs that will be introduced to the market allowing for safe and optimal dosing across a wide range of pharmaceuticals. In this review, we report on the recent developments in biosensing and nanobiosensing techniques and, focussing mainly on anti-cancer agents and antibiotics, we discuss the different classes of molecules upon which therapeutic drug monitoring has already been successfully applied. The potential contributions of (nano)biosensors are also reviewed for the emerging areas of therapeutic response monitoring, where markers are monitored to ensure compliance of a patient to a treatment and in the area of cellular response to therapeutic drugs in order to identify cytotoxic effects of drugs on cells or to identify patients responding to a drug. [ABSTRACT FROM AUTHOR]

Characterization of protein adsorption to surfaces has implications from biosensing to protective biocoatings. While research studies have principally focused on determining the magnitude of protein adsorption to surfaces, the proteins involved in the process remains only broadly identified and has not been investigated on several surfaces. To further elucidate the nonspecific adsorption process of serum to surfaces, surface plasmon resonance (SPR) and matrix assisted laser desorption ionization mass spectrometry (MALDI-MS) were used in combination to obtain quantitative and qualitative information about the process of protein adsorption to surfaces. To validate the technique, crude serum was nonspecifically adsorbed on four self-assembled monolayer (SAM) on gold: 16-mercaptohexadecanoic add (16-MHA), 1l-mercaptoundecane(ethyiene glycol)3-COOH (PEG), 3-MPA-LHDLHD-OH, and 3-MPA-HHHDD-OH. Direct MS analysis of the nonspecifically adsorbed proteins suggested the presence of a variety of protein (BSA, IgG, and apolipoprotein A-l). Performing a trypsin digestion of the nonspecifically adsorbed proteins confirmed the presence of BSA and apolipoprotein A-1 and further revealed the complexity of the process by detecting the presence of complement C3, SHC-transforming protein 1, and kininogen 2. The level of nonspecific adsorption on different surfaces measured by SPR sensing directly correlated with the intensity of the serum protein and indirectly with the tryptic peptides measured by MS. Detailed analysis of the BSA peptides digested on 16-MHA and for BSA digested in solution was used to investigate the orientation of BSA on this surface. The combination of SPR and MS allows the quantitative and qualitative understanding of protein adsorption processes to surfaces. [ABSTRACT FROM AUTHOR]

Metallic thin films patterned with micrometer size triangle or hole arrays present plasmonic properties when excited in the Kretschmann configuration, that are improved in comparison to conventional thin film surface plasmon resonance (SPR). These optical properties can be tuned by varying the physical aspects of the microplasmonic structures. Triangles and microhole arrays were prepared with modified nanosphere lithography (NSL) using latex spheres of 0.65, 0.82, 1.0, 1.5, or 3.2 pm in diameter. This allowed the preparation of triangles with edge lengths between 275 to 2000 nm and microhole arrays of various periodicities, diameters, and hole depths. These microstructures were studied to understand the relationship between the physical aspects and the optical properties, such as the sensitivity, working refractive index range, spectral width of the plasmonic peaks, spectral noise, and refractive index resolution. Microhole arrays with a hole diameter equal to half the periodicity were found to combine the advantages of both localized surface plasmon resonance (LSPR) on nanoparticles and SPR on a thin film. These microhole arrays exhibited high sensitivity to refractive index (>3000 nm/RIU), sensitivity to monolayer formation (2-fold improvement compared to thin films), and excellent refractive index resolution (10-6 RIU). Finally, a biosensor for the detection of 10 nM of immunoglobulin G (lgG) exhibited a greater response with microplasmonic materials compared to conventional thin Au films. Hence, these novel plasmonic materials exhibit a strong potential as an SPR sensing platform. They can be implemented on existing insinimentation and use detection protocols developed for current SPR sensors. [ABSTRACT FROM AUTHOR]

Near-zero fouling monolayers based on binaiy patterned peptides allow low nanomolar detection of the matrix metalloproteinase-3 (MMP-3) directly in crude bovine serum, without sample pretreatment, secondary antibody detection or signal amplification. The peptide 3-MPA-HHHDD-OH (3-MPA, 3-mercaptopropionic acid) was found optimal compared to other binary patterned peptides based on 3-MPA-Ax-By-OH, where 0 ⩽ x, y ⩽ 5, and x + y = 5, and compared to PEG. In this study, amino acid A was His, Asp, Ser, or Leu, and amino acid B was His, Asp, or Ser. Zwitterionic peptides and other peptides exhibited excellent resistance to non-specific adsorption. Binary patterned peptides were capped with 3-MPA on the N-terminus providing a monolayer with the C-terminus carboxylic acid available to subsequently immobilize antibodies. Thereby, an IgG biosensor demonstrated the efficiency of binary patterned peptides in SPR biosensingwith a detection limit of 1-10 μM In PBS, similar to other optical or electrochemical techniques. This protocol was applied to establish a calibration curve for MMP-3, an analyte of clinical interest for many pathologies and a potential indicator of cancer. The LOD for MMP-3 was 0.14 nM in PBS, with a linearity of up to 50 nM. With the use of PBS calibration, MMP-3 was quantified at low nanomolar in undiluted bovine serum. The SPR response in serum was statistically the same as in PBS. A sensor exposed to blank serum exhibited negligible nonspecific adsorption. Hence, binary patterned peptides are suitable for bio-sensing directly in complex biological matrixes. [ABSTRACT FROM AUTHOR]

This manuscript addresses two issues with calibration of surface plasmon resonance sensors which can track refractive index changes to measure correlated bulk properties. First, employing non-air references do not return the traditional parabolic dip in the SPR spectra; instead the returned SPR spectra are more ‘derivative’ in shape. Investigated are five different ways to calibrate SPR spectra when non-air references are employed. The minimum hunt method (MHM) calculates the position of this minimum by fitting a parabola to the curve. MHM is shown to consistently achieve prediction errors of 3×10-4 RI units (RIU) using an air reference and a RI calibration set of aqueous sucrose samples measured with an Abbé refractometer accurate to 1×10-4 RIU. Use of principal component regression (PCR) with air or water references generates prediction errors at best the same as MHM but worse as the concentration range of samples increases. Second, a method for calibrating SPR spectra across a wide temperature range is presented. It is shown that this method is capable of successfully mitigating the effect of temperature drifts up to 20 °C. MHM was subsequently used to predict the concentration of 0.00–6.99 wt.% KCl(aq) samples between 6 and 29 °C, a range found in surface ocean waters. Prediction error as small as 0.073 wt.% correlates to 2×10-4 RIU shows MHM holds over a wide dynamic range. [Copyright &y& Elsevier]

SARS-CoV-2 variants of concern (VOCs) have emerged worldwide, with implications on the spread of the pandemic. Characterizing the cross-reactivity of antibodies against these VOCs is necessary to understand the humoral response of non-hospitalized individuals previously infected with SARS-CoV-2, a population that remains understudied. Thirty-two SARS-CoV-2-positive (PCR-confirmed) and non-hospitalized Canadian adults were enrolled 14–21 days post-diagnosis in 2020, before the emergence of the B.1.351 (also known as Beta), B.1.617.2 (Delta) and P.1 (Gamma) VOCs. Sera were collected 4 and 16 weeks post-diagnosis. Antibody levels and pseudo-neutralization of the ectodomain of SARS-CoV-2 spike protein/human ACE-2 receptor interaction were analyzed with native, B.1.351, B.1.617.2 and P.1 variant spike proteins. Despite a lower response observed for the variant spike proteins, we report evidence of a sustained humoral response against native, B.1.351, B.1.617.2 and P.1 variant spike proteins among non-hospitalized Canadian adults. Furthermore, this response inhibited the interaction between the spike proteins from the different VOCs and ACE-2 receptor for ≥ 16 weeks post-diagnosis, except for individuals aged 18–49 years who showed no inhibition of the interaction between B.1.617.1 or B.1.617.2 spike and ACE-2. Interestingly, the affinity (KD) measured between the spike proteins (native, B.1.351, B.1.617.2 and P.1) and antibodies elicited in sera of infected and vaccinated (BNT162b2 and ChAdOx1 nCoV-19) individuals was invariant. Relative to sera from vaccine-naïve (and previously infected) individuals, sera from vaccinated individuals had higher antibody levels (as measured with label-free SPR) and more efficiently inhibited the spike–ACE-2 interactions, even among individuals aged 18–49 years, showing the effectiveness of vaccination. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 variants of concern (VOCs) have emerged worldwide, with implications on the spread of the pandemic. Characterizing the cross-reactivity of antibodies against these VOCs is necessary to understand the humoral response of non-hospitalized individuals previously infected with SARS-CoV-2, a population that remains understudied. Thirty-two SARS-CoV-2-positive (PCR-confirmed) and non-hospitalized Canadian adults were enrolled 14–21 days post-diagnosis in 2020, before the emergence of the B.1.351 (also known as Beta), B.1.617.2 (Delta) and P.1 (Gamma) VOCs. Sera were collected 4 and 16 weeks post-diagnosis. Antibody levels and pseudo-neutralization of the ectodomain of SARS-CoV-2 spike protein/human ACE-2 receptor interaction were analyzed with native, B.1.351, B.1.617.2 and P.1 variant spike proteins. Despite a lower response observed for the variant spike proteins, we report evidence of a sustained humoral response against native, B.1.351, B.1.617.2 and P.1 variant spike proteins among non-hospitalized Canadian adults. Furthermore, this response inhibited the interaction between the spike proteins from the different VOCs and ACE-2 receptor for ≥ 16 weeks post-diagnosis, except for individuals aged 18–49 years who showed no inhibition of the interaction between B.1.617.1 or B.1.617.2 spike and ACE-2. Interestingly, the affinity (KD) measured between the spike proteins (native, B.1.351, B.1.617.2 and P.1) and antibodies elicited in sera of infected and vaccinated (BNT162b2 and ChAdOx1 nCoV-19) individuals was invariant. Relative to sera from vaccine-naïve (and previously infected) individuals, sera from vaccinated individuals had higher antibody levels (as measured with label-free SPR) and more efficiently inhibited the spike–ACE-2 interactions, even among individuals aged 18–49 years, showing the effectiveness of vaccination. [ABSTRACT FROM AUTHOR]

The use of nanoparticle-based colorimetric methods has received considerable attention in a broad range of clinical and biomedical applications due to their high sensitivity, low cost, extreme simplicity and excellent analytical performance. However, the formation of a protein corona has severely limited the application of nanoparticles (NPs) in clinical samples, which can confer colloidal stability to serum-exposed nanoparticles compared to pristine particles. To address this challenge, dialysis, ultrafiltration and phenol : chloroform : isopentanol extraction methods were compared aiming at facile and routine protein separation methods to eliminate the formation of protein corona on NPs and the development of a sensitive and simple therapeutic drug monitoring (TDM) assay for the detection of aminoglycoside antibiotics in serum. Based on the comparison of the sensitivity of the localized surface plasmon resonance (LSPR) aggregation assay in pure water, untreated serum and serum after the different sample preparation methods, we revealed by Coomassie blue staining that proteins in the serum were the predominant interfering molecules to degrade the sensitivity of serum-based aggregation assays. Using dialysis, naked eye semi-quantification was achieved at the clinical level for amikacin, tobramycin and streptomycin. The dialysis efficiency and dialysis coefficient of amikacin were also measured to prove the efficacy of dialysis as a fast and efficient protein-removal method. This strategy is expected to be applicable universally as a pretreatment for the assay of small molecules with plasmonic assays in crude biological samples. [ABSTRACT FROM AUTHOR]

We report the integration of surface plasmon resonance (SPR), cyclic voltammetry and electrochemiluminescence (ECL) responses to survey the interfacial adsorption and energy transfer processes involved in ECL on a plasmonic substrate. It was observed that a Tween 80/tripropylamine nonionic layer formed on the gold electrode of the SPR sensor, while enhancing the ECL emission process, affects the electron transfer process to the luminophore, Ru(bpy)32+, which in turn has an impact on the plasmon resonance. Concomitantly, the surface plasmon modulated the ECL intensity, which decreased by about 40 %, due to an interaction between the excited state of Ru(bpy)32+ and the plasmon. This occurred only when the plasmon was excited, demonstrating that the optically excited surface plasmon leads to lower plasmon‐mediated luminescence and that the plasmon interacts with the excited state of Ru(bpy)32+ within a very thin layer. [ABSTRACT FROM AUTHOR]

We report the integration of surface plasmon resonance (SPR), cyclic voltammetry and electrochemiluminescence (ECL) responses to survey the interfacial adsorption and energy transfer processes involved in ECL on a plasmonic substrate. It was observed that a Tween 80/tripropylamine nonionic layer formed on the gold electrode of the SPR sensor, while enhancing the ECL emission process, affects the electron transfer process to the luminophore, Ru(bpy)32+, which in turn has an impact on the plasmon resonance. Concomitantly, the surface plasmon modulated the ECL intensity, which decreased by about 40 %, due to an interaction between the excited state of Ru(bpy)32+ and the plasmon. This occurred only when the plasmon was excited, demonstrating that the optically excited surface plasmon leads to lower plasmon‐mediated luminescence and that the plasmon interacts with the excited state of Ru(bpy)32+ within a very thin layer. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • FeOx overcome single crystal phases generally suffering from serious agglomeration and poor electrical conductivity. • The synergistic effect between the electrocatalytic property and the polycrystalline structure of FeOx was verified. • Hybrid FeOx with variable oxidation states remarkably facilitate the efficient redox charge transfer. Abstract Investigations on interplay between sensing platform performance and crystal phase of material are the new beginning of designing advanced bioanalytical systems. Herein, FeO x nanoparticles (NPs, ∼100 nm), including superfine magnetic (Fe 3 O 4) and hematite (α-Fe 2 O 3) nanocrystals in single particles, have been employed to verify the synergistic effect between the electrocatalytic property and the polycrystalline structure of the materials. Moreover, this strategy overcomes that single crystal phases generally suffer from serious agglomeration and poor electrical conductivity. More importantly, hybrid metal oxides (e.g., α-Fe 2 O 3 /Fe 3 O 4) with variable oxidation states remarkably facilitate the efficient redox charge transfer. Taking the detection of Flutamide (FLT) in prostate cancer cells (VCaP cells) as example, the dynamic ranges of the oxidation states from the different crystal phases were integrated into a single electrochemical sensor interface. Furthermore, good selectivity, accuracy, satisfactory sensitivity (769.1 μA mM−1 cm-2) and low detection limits (46.6 nM) were achieved. Going beyond the conventional single-crystal phase-driven electrochemical sensing, the elaborate of polycrystalline structure in a single particle may open a new approach for the design of outstanding electrode materials, which not only can significantly improve the performance of sensing platforms, but also can be used to rationally design the material properties according to the applications. [ABSTRACT FROM AUTHOR]

A highly sensitive surface plasmon resonance (SPR) sensor is reported for glucose detection using self-assembled p-mercaptophenylboronic acid (PMBA) monolayer on Au coated optical fibers. The cis-diol group of saccharides, such as for glucose, interacted with the self-assembled PMBA monolayers on the optical fibers, but the low molecular mass of glucose is insufficient for measuring a significant shift in SPR wavelength. The response for glucose was thus enhanced with Au nanoparticles (Au NPs) modified with 2-aminoethanethiol (AET) and PMBA. Selectivity was assured since glucose has the ability to capture the signal amplification tags (Au NPs/AET- PMBA) through secondary binding with another set of syn-periplanar diol groups and the PMBA on the gold surface. Accordingly, a glucose concentration-dependent sandwich structure was formed and the coupling between Au NPs and Au film results in the red shift of SPR resonance wavelength. The experimental results demonstrated that this SPR sensor responded to glucose within a range of 0.01–30 mM better than to fructose and galactose. The minimum concentration for quantify glucose is as low as 80 nM, which is lower than the physiological blood glucose level. Glucose was then accurately detected in urine sample, which indicated the potential application of the sensor for the analysis of glucose in urine. We believe that our proposed PMBA-modified single amplification tag and sensing principle can also be used for biomolecules consisting of carbohydrate structures, particularly for DNA-associated bioanalysis. [ABSTRACT FROM AUTHOR]

MicroRNA (miRNA) sensing, especially the miRNA-200 family, is increasingly targeted for cancer diagnostics. As the sensing schemes often rely on nanoparticles functionalized with a specific oligonucleotide, we investigate the hydribization conditions using the common case of surface plasmon resonance (SPR) sensing of miRNA and a gold nanoparticle (Au NP) competitor. In this type of assays, the Au NPs compete with the microRNA to bind the capture probe immobilized on the gold surface. In our study, we simplify and improve the detection procedure by adopting 11-mercaptoundecanoic acid (11-MUA) as linker to the gold surface, not only omitting the blocking step of 6-mercapto-1-hexanol (MCH), but also increasing the probe density. We report that the response in our SPR sensing studies increased with the size of Au NPs according to the plasmon ruler equation, but the larger AuNPs of 32 nm lacked colloidal stability. In addition, decreasing the ratio of oligonucleotide to Au NPs and the addition of polyethylene glycol (PEG) to hybridization buffer also favored a better response in SPR sensing of miRNA. The optimization led to an improved detection sensitivity in our competition method and a detection limit as low as 500 pM for miRNA-200b without amplification of miRNA and use of other amplification schemes. [ABSTRACT FROM AUTHOR]

2D nanoplasmonic substrates excited in transmission spectroscopy are ideal for several biosensing, metamaterial, and optical applications. We show that their excellent properties can be further improved with plasmonic coupling of Au nanoparticles (AuNPs) on gold-coated nanodisk arrays excited at large incidence angles of up to 50°. The Bragg modes (BM) thereby strongly couple to AuNP immobilized on the plasmonic substrate due to shorter decay length of the plasmon at higher incidence angles, leading to a further enhanced field between the AuNP and the plasmonic substrate. The field was highest and two hotspots were created at orthogonal positions for AuNP located close to the corner of the Au film and Au nanodisk, which was also observed for AuNP dimers. Hybridization between single-stranded DNA (ssDNA) immobilized on the surface of the AuNPs and the capture ssDNA on the gold-coated nanodisk arrays led to at least a 5-fold signal improvement and a 7-fold lower limit of detection at 7 pM for ssDNA-functionalized AuNPs at large incident angles. Thus, we demonstrate that higher field strength can be accessed and the significant advantages of working with high incidence angles with AuNP on a 2D plasmonic crystal in plasmonic sensing. [ABSTRACT FROM AUTHOR]

A field-deployable surface plasmon resonance (SPR) sensor is reported for the detection of the energetic material (commonly termed explosives) 1,3,5-trinitroperhydro-1,3,5-triazine (RDX) at ppb concentration in environmental samples. The SPR sensor was first validated under laboratory conditions with uncontaminated natural water samples spiked with known concentrations of RDX near the EPA limit of 2 ppb, which was then applied to monitor environmental samples collected in different downgradient wells near a grenade training range. The SPR sensor was finally tested on the field, where environmental samples were analysed on location in less than 90 minutes per well, which included the time to setup the equipment, sample the well and analyse the sample. The SPR analysis time was less than 45 minutes for equilibration, recalibration and measuring the water sample. Results obtained with the SPR sensors were cross-validated with the standard HPLC method (EPA method 8330b), and they showed good agreement with an accuracy within less than 1.6 ppb for analysis at the sampling sites, and with the relative standard deviation (RSD) better than 20% for field and laboratory measurements. The SPR sensor worked in a range of environmental conditions, including operation from about 0 °C to nearly 30 °C. The instrument was easily deployed near the sampling site using motor vehicles under summer conditions (Lab-in-a-Jeep) and using a sled under winter conditions (Lab-on-a-sled), showcasing the field deployability of the RDX SPR sensor and the possibility of continuously monitoring RDX in the environment. [ABSTRACT FROM AUTHOR]

In this paper, we report a novel wavelength interrogation-based surface plasmon resonance (SPR) system, in which a film of three Ag layers and three Au layers are alternately deposited on a Kretschmann configuration as sensing element. This multilayer film shows higher sensitivity for refractive index (RI) measurement by comparing with single Au layer structure, which is consistent with its theoretical calculation. A sensitivity range of 2056-5893 nm/RIU can be achieved, which is comparable to RI sensitivities of other wavelength-modulated SPR sensors. Compared with Ag film, this Ag/Au multilayer arrangement offers anti-oxidant protection. This SPR biosensor based on a cost-effective Ag/Au multilayer structure is applicable to the real-time detection of specific interactions and dissociation of low protein concentrations. To extend the application of this highly-sensitive metal film device, we integrated this concept on an optical fiber. The range of RI sensitivities with Ag/Au multilayer was 1847-3309 nm/RIU. This miniaturized Ag/Au multilayer-based fiber optic sensor has a broad application in chemical and biological sensing. [ABSTRACT FROM AUTHOR]

Aminoglycoside antibiotics are used in the treatment of infections caused by Gram-negative bacteria, and are often dispensed only in severe cases due to their adverse side effects. Patients undergoing treatment with these antibiotics are therefore commonly subjected to therapeutic drug monitoring (TDM) to ensure a safe and effective personalised dosage. The ability to detect these antibiotics in a rapid and sensitive manner in human fluids is therefore of the utmost importance in order to provide effective monitoring of these drugs, which could potentially allow for a more widespread use of this class of antibiotics. Herein, we report on the detection of various aminoglycosides, by exploiting their ability to aggregate gold nanoparticles. The number and position of the amino groups of aminoglycoside antibiotics controlled the aggregation process. We investigated the complementary techniques of surface enhanced Raman spectroscopy (SERS) and localized surface plasmon resonance (LSPR) for dual detection of these aminoglycoside antibiotics and performed an in-depth study of the feasibility of carrying out TDM of tobramycin using a platform amenable to high throughput analysis. Herein, we also demonstrate dual detection of tobramycin using both LSPR and SERS in a single platform and within the clinically relevant concentration range needed for TDM of this particular aminoglycoside. Additionally we provide evidence that tobramycin can be detected in spiked human serum using only functionalised nanoparticles and SERS analysis. [ABSTRACT FROM AUTHOR]

Identification and quantification of proteins in imaging of biological samples are a challenge in today's science. Here, we demonstrate a novel surface plasmon resonance imaging-matrix assisted laser desorption ionization imaging mass spectrometry (SPRi-MALDI IMS) coupled technique competent for the acquisition of multiparametric information by creating a tissue section imprint on an SPRi sensor surface. Correlated images were acquired in SPRi and in MALDI IMS for abundant proteins from a single mouse kidney tissue. The spatial organization of the transferred proteins from the tissue to the SPRi surface was preserved and imaged by SPR and MALDI MS. Surface chemistry was selected to nonspecifically adsorb and retain high concentrations of proteins on the SPRi surface. The diffusion kinetics were controlled to ensure fast transfer of proteins from the tissue sections with minimal lateral diffusion to achieve high spatial fidelity transfer. Lastly, the SPRi instrument was modified to insert a tissue sample in the fluidics chamber to facilitate the real-time measurement of the transfer process. The MALDI IMS experimental conditions, such as matrix deposition and the interface between the SPRi prism and the MALDI IMS instrument, were also optimized. The results show quantitative and regioselective SPRi images correlating to MALDI IMS images of different proteins transferred from a single tissue section. [ABSTRACT FROM AUTHOR]

We report that a shorter Debye length and, as a consequence, decreased colloidal stability are required for the molecular interaction of folic acid-modified Au nanoparticles (Au NPs) to occur on a surface-bound receptor, human dihydrofolate reductase (hDHFR). The interaction measured using surface plasmon resonance (SPR) sensing was optimal in a phosphate buffer at pH 6 and ionic strength exceeding 300 mM. Under these conditions, the aggregation constant of the Au NPs was approximately 104 M−1 s−1 and the Debye length was below 1 nm, on the same length scale as the size of the folate anion (approximately 0.8 nm). Longer Debye lengths led to poorer SPR responses, revealing a reduced affinity of the folic acid-modified Au NPs for hDHFR. While high colloidal stability of Au NPs is desired in most applications, these conditions may hinder molecular interactions due to Debye lengths exceeding the size of the ligand and thus preventing close interactions with the surface-bound molecular receptor. [ABSTRACT FROM AUTHOR]

In this paper, the coupling interaction is investigated between a metallic nanowire array and a metal film under the Kretschmann condition. The plasmonic multilayer is composed of a metallic nanowire array embedded in a polymer layer positioned above a metal film, exploiting the classical surface plasmon resonance (SPR) configuration. We analyze the influence of various structural parameters of the metallic nanowire array on the SPR spectrum of thin metal film. The results show that the coupling interactions of nanowires with the metal film can greatly affect SPR resonance wavelength and increase SPR sensitivity. The coupling strength of metallic nanowire array and metal film also impacts resonance wavelength, which can be used to adjust SPR range but have little effect on its sensitivity. The results are confirmed using a dipole coupling resonance model of metallic nanowire. We demonstrated that this nanostructured hybrid structure can be used for high sensitivity SPR monitoring in a large spectral range, which is important for advanced SPR measurement including fiber-optic SPR sensing technology. [ABSTRACT FROM AUTHOR]

Ionic liquid self-assembled monolayers (SAM) were designed and applied for binding streptavidin, promoting affinity biosensing and enzyme activity on gold surfaces of sensors. The synthesis of 1-((+)-biotin)pentanamido)propyl)-3-(12-mercaptododecyl)-imidazolium bromide, a biotinylated ionic liquid (IL-biotin), which self-assembles on gold film, afforded streptavidin sensing with surface plasmon resonance (SPR). The IL-biotin-SAM efficiently formed a full streptavidin monolayer. The synthesis of 1-(carboxymethyl)-3-(mercaptododecyl)-imidazoliumbromide, a carboxylated IL (IL-COOH), was used to immobilize anti-IgG to create an affinity biosensor. The IL-COOH demonstrated efficient detection of IgG in the nanomolar concentration range, similar to the alkylthiols SAM and PEG. In addition, the IL-COOH demonstrated low fouling in crude serum, to a level equivalent to PEG. The IL-COOH was further modified with N,N'-bis (carboxymethyl)-l-lysine hydrate to bind copper ions and then, chelate histidine-tagged biomolecules. Human dihydrofolate reductase (hDHFR) was chelated to the modified IL-COOH. By monitoring enzyme activity in situ on the SPR sensor, it was revealed that the IL-COOH SAM improved the activity of hDHFR by 24% in comparison to classical SAM. Thereby, IL-SAM has been synthesized and successfully applied to three important biosensing schemes, demonstrating the advantages of this new class of monolayers. [ABSTRACT FROM AUTHOR]

These authors contributed equally: Maryam Hojjat Jodaylami, Abdelhadi Djaïleb and Pierre Ricard. Correction to: I Scientific Reports i https://doi.org/10.1038/s41598-021-00844-z, published online 08 November 2021 The original version of this Article contained an error in the spelling of the author Stella Cellier-Goetghebeur which was incorrectly given as Stella Cellier-Goethebeur. [Extracted from the article]

Abstract: We validate, by comparison with experimental data, a theoretical description of the amperometric response of microbiosensors formed via enzyme entrapment. The utility of the theory is further illustrated with two relevant examples supported by experiments: (1) quantitative detection of glucose and (2) quantitative detection of adenosine triphosphate (ATP). [Copyright &y& Elsevier]

Abstract: We have developed a theoretical description of the amperometric response of ultramicroelectrode (UME) biosensors formed via enzyme entrapment. Our model allows for multiple enzymes and co-substrates, and results in a closed-form analytical expression for the steady-state current response of the disk ultramicroelectrode. It captures the effects of enzyme-entrapment domain size, species transport properties (which can be different in the polymer and surrounding electrolyte), enzyme kinetics, and axisymmetric diffusion. Assumptions inherent in the derivation are carefully explained, as are the resulting limits on the applicability of the results. The ability to theoretically predict the response of enzyme entrapped UMEs should enable improved design, operation, and data interpretation for this important class of biosensors. [Copyright &y& Elsevier]

• An optical fiber LSPR biosensor via diblock copolymer-templated AuNRs monolayer was reported. • PS- b -PV4P-templated citrate-AuNR film led to higher RI sensitivity than that of PS- b -PAA-templated CTAB-AuNR film. • PS- b -PV4P-templated biosensor exhibited better spectral characteristics than polyelectrolyte and APTES-based biosensors. • PS- b -PV4P-templated biosensor exhibited an excellent response to human IgG with LOD of 0.6 nM. Block copolymer (BCP) brush-like layer absorbed on optical fibers are shown to address the longstanding challenge of forming dense and well-dispersed gold nanorods (AuNRs) films on highly curved surface, allowing the development of real-time localized surface plasmon resonance (LSPR) biosensors for antigen-antibody interaction. This method requires only solution-based manufacturing processes and a plasma cleaning step to self-assemble AuNRs with various aspect ratios on the optical fibers. Because AuNRs capped with cetyltrimethylammonium bromide (CTAB) have been problematic for biosensing applications due to their cytotoxicity and displacement difficulty in the construction of biosensors, citrate-stabilized AuNRs were prepared from CTAB-stabilized AuNRs via surfactant exchange. For comparison, both a poly(styrene)- b -poly(acrylic acid) (PS- b -PAA) BCP template with CTAB-stabilized AuNRs and a poly(styrene)- b -poly(4-vinyl pyridine) (PS- b -P4VP) BCP template with citrate-stabilized AuNRs were employed for the fabrication of the optical fiber biosensor. The LSPR spectral analysis results demonstrate that the sensitivity of the sensor produced by the PS- b -P4VP templating method was 1.5 times better than that of the sensor produced by the PS- b -PAA templating method, which was due to the improved surface coverage and reduced aggregation of nanoparticles. The detection limit of the PS- b -P4VP-templated sensor for human IgG was 0.6 nM. Furthermore, for citrate-stabilized AuNRs, the PS- b -P4VP templating method also led to a better surface morphology and higher sensitivity as compared to the standard particle absorption methods using alkoxysilanes or polyelectrolytes on identical fibers. The simplicity of the fabrication process and the far superior optical performance of the PS- b -P4VP-templated LSPR optical fiber sensor illustrate the ability to regulate the detection range by tuning the aspect ratios of the AuNRs, and demonstrate its application prospects as a real-time biosensor without cytotoxicity. [ABSTRACT FROM AUTHOR]

Mapping the transition of Ag nanotriangle to nanohole arrays revealed that the optimal SERS response was obtained near the transition. Correlated AFM and Raman imaging provided novel experimental proof that hot spots are located on Ag islands for nanotriangle arrays and in the core area of the hole for nanohole arrays, which is in agreement with previous theoretical predictions. [ABSTRACT FROM AUTHOR]