Brownian Motion Governs the Plasmonic Enhancement of Colloidal Upconverting Nanoparticles.

Upconverting nanoparticles are essential in modern photonics due to their ability to convert infrared light to visible light. Despite their significance, they exhibit limited brightness, a key drawback that can be addressed by combining them with plasmonic nanoparticles. Plasmon-enhanced upconversion has been widely demonstrated in dry environments, where upconverting nanoparticles are immobilized, but constitutes a challenge in liquid media where Brownian motion competes against immobilization. This study employs optical tweezers for the three-dimensional manipulation of an individual upconverting nanoparticle, enabling the exploration of plasmon-enhanced upconversion luminescence in water. Contrary to expectation, experiments reveal a long-range (micrometer scale) and moderate (20%) enhancement in upconversion luminescence due to the plasmonic resonances of gold nanostructures. Comparison between experiments and numerical simulations evidences the key role of Brownian motion. It is demonstrated how the three-dimensional Brownian fluctuations of the upconverting nanoparticle lead to an "average effect" that explains the magnitude and spatial extension of luminescence enhancement.

The Past and the Future of Langmuir and Langmuir-Blodgett Films.

The Langmuir-Blodgett (LB) technique, through which monolayers are transferred from the air/water interface onto a solid substrate, was the first method to allow for the controlled assembly of organic molecules. With its almost 100 year history, it has been the inspiration for most methods to functionalize surfaces and produce nanocoatings, in addition to serving to explore concepts in molecular electronics and nanoarchitectonics. This paper provides an overview of the history of Langmuir monolayers and LB films, including the potential use in devices and a discussion on why LB films are seldom considered for practical applications today. Emphasis is then given to two areas where these films offer unique opportunities, namely, in mimicking cell membrane models and exploiting nanoarchitectonics concepts to produce sensors, investigate molecular recognitions, and assemble molecular machines. The most promising topics for the short- and long-term prospects of the LB technique are also highlighted.

In situ interaction between the hormone 17α-ethynylestradiol and the liquid-ordered phase composed of the lipid rafts sphingomyelin and cholesterol.

Hormone treatments are frequently associated with cardiovascular diseases and cancers in women. Additionally, the detrimental effects of their presence as contaminants in water remain a concern. The transport of hormones through cell membranes is essential for their biological action, but investigating cell permeability is challenging owing to the experimental difficulty in dealing with whole cells. In this paper, we study the interaction of the synthetic hormone 17α-ethynylestradiol (EE2) with membrane models containing the key raft components sphingomyelin (SM) and cholesterol (Chol). The models consisted of Langmuir monolayers and giant unilamellar vesicles (GUVs) that represent bilayers. EE2 induced expansion of SM monolayers upon interacting with the non-hydrated amide group of SM head, but it had practically no effect on SM GUVs because these group are not available for interaction in bilayers. In contrast, EE2 interacted with hydrated phosphate group (PO2-) and amide group of SM/Chol mixture monolayer, which could explain the loss in phase contrast of liquid-ordered GUVs suggesting pore formation. A comparison with reported EE2 effects on GUVs in the fluid phase, for which no loss in phase contrast was observed, indicates that the liquid-ordered phase consisting of lipid rafts is relevant to be associated with the changes on cell permeability caused by the hormones.

Magnetochiroptical nanocavities in hyperbolic metamaterials enable sensing down to the few-molecule level.

In this work, we combine the concepts of magnetic circular dichroism, nanocavities, and magneto-optical hyperbolic metamaterials (MO-HMMs) to demonstrate an approach for sensing down to a few molecules. Our proposal comprises a multilayer MO-HMM with a square, two-dimensional arrangement of nanocavities. The magnetization of the system is considered in polar configuration, i.e., in the plane of polarization and perpendicular to the plane of the multilayer structure. This allows for magneto-optical chirality to be induced through the polar magneto-optical Kerr effect, which is exhibited by reflected light from the nanostructure. Numerical analyses under the magnetization saturation condition indicate that magnetic circular dichroism peaks can be used instead of reflectance dips to monitor refractive index changes in the analyte region. Significantly, we obtained a relatively high sensitivity value of S = 40 nm/RIU for the case where refractive index changes are limited to the volume inside nanocavities, i.e., in the limit of a few molecules (or ultralow concentrations), while a very large sensitivity of S = 532 nm/RIU is calculated for the analyte region distributed along the entire superstrate layer.

Electrochemical immunosensors using electrodeposited gold nanostructures for detecting the S proteins from SARS-CoV and SARS-CoV-2.

This paper reports the development of a low-cost (< US$ 0.03 per device) immunosensor based on gold-modified screen-printed carbon electrodes (SPCEs). As a proof of concept, the immunosensor was tested for a fast and sensitive determination of S proteins from both SARS-CoV and SARS-CoV-2, by a single disposable device. Gold nanoparticles were electrochemically deposited via direct reduction of gold ions on the electrode using amperometry. Capture antibodies from spike (S) protein were covalently immobilized on carboxylic groups of self-assembled monolayers (SAM) of mercaptoacetic acid (MAA) attached to the gold nanoparticles. Label-free detection of S proteins from both SARS-CoV and SARS-CoV-2 was performed with electrochemical impedance spectroscopy (EIS). The immunosensor fabricated with 9 s gold deposition had a high performance in terms of selectivity, sensitivity, and low limit of detection (LOD) (3.16 pmol L-1), thus permitting the direct determination of the target proteins in spiked saliva samples. The complete analysis can be carried out within 35 min using a simple one-step assay protocol with small sample volumes (10 µL). With such features, the immunoplatform presented here can be deployed for mass testing in point-of-care settings.

Anti-aquaporin-4 immunoglobulin G colorimetric detection by silver nanoparticles.

Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory and autoimmune disease whose biomarker is the anti-AQP4-IgG autoantibody that binds to aquaporin-4 (AQP4) protein. We introduced a nanosensor with a sensitivity of 84.6%, higher than the CBA's 76.5%. Using silver nanoparticles (AgNPs), we detected not only seropositive but also some false-negative patients previously classified with CBA. It consisted of AgNPs coated with one of a panel of 5 AQP4 epitopes. The ability in detecting the anti-AQP4-IgG in NMOSD patients depended on the epitope and synergy could be obtained by combining different epitopes. We demonstrated that NMOSD patients could easily be distinguished from healthy subjects and patients with multiple sclerosis. Using the most sensitive AQP461-70 peptide, we established a calibration curve to estimate the concentration of anti-AQP4-IgG in seropositive NMOSD patients. The ability to enhance the accuracy of the diagnosis may improve the prognosis of 10-27% of anti-AQP4-IgG seronegative patients worldwide.

Investigation of Chloroquine Resinate Feasibility and In Vitro Taste Masking Evaluation for Pediatric Formulations.

In this study, chloroquine resinates were prepared at a 1:1 (w:w) drug-to-resin ratio using the batch method with polacrilex (PC), sodium polystyrene sulfonate (SPS), and polacrilin potassium (PP) ion exchange resins (IER). The influence of drug/resin ratio and pH of the medium on drug loading efficiency was explored. UV-VIS spectrophotometric analysis showed that SPS resin had high loading efficiency for chloroquine diphosphate (CLP), above 89%, regardless of the pH. PP resin was more effective at pH 5.0 (90.68%) than at pH 1.0 (2.09%), and PC resin had only 27.63% of CLP loading efficiency. CLP complexation with IER yielded amorphous mixtures according to results from differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD), thus indicating drug-resin interaction. The taste masking efficiency was evaluated with in vitro methods using an adapted dissolution test and an electronic tongue system. During dissolution tests, SPS released only 1.0% of CLP after 300 s, while PP released over 10% after 90 s in simulated saliva solution. The electronic tongue distinguished the samples containing CLP, resins, and resinates by using multidimensional projection techniques that indicated an effective drug taste masking. In an accelerated stability study, the drug contents did not decrease in chloroquine resinates, and there was no physical degradation of the resinates after 60 days. Using chloroquine resinates therefore represents a novel way to evaluate taste masking in vitro which is relevant for the early formulation development process.

Erratum: Toward Lossless Infrared Optical Trapping of Small Nanoparticles Using Nonradiative Anapole Modes [Phys. Rev. Lett. 127, 186803 (2021)].

This corrects the article DOI: 10.1103/PhysRevLett.127.186803.

Toward Lossless Infrared Optical Trapping of Small Nanoparticles Using Nonradiative Anapole Modes.

A challenge in plasmonic trapping of small nanoparticles is the heating due to the Joule effect of metallic components. This heating can be avoided with electromagnetic field confinement in high-refractive-index materials, but nanoparticle trapping is difficult because the electromagnetic fields are mostly confined inside the dielectric nanostructures. Herein, we present the design of an all-dielectric platform to capture small dielectric nanoparticles without heating the nanostructure. It consists of a Si nanodisk engineered to exhibit the second-order anapole mode at the infrared regime (λ=980 nm), where Si has negligible losses, with a slot at the center. A strong electromagnetic hot spot is created, thus allowing us to capture nanoparticles as small as 20 nm. The numerical calculations indicate that optical trapping in these all-dielectric nanostructures occurs without heating only in the infrared, since for visible wavelengths the heating levels are similar to those in plasmonic nanostructures.

Lipid-matrix effects on tyrosinase immobilization in Langmuir and Langmuir-Blodgett films.

The immobilization of the enzyme tyrosinase (Tyr) in lipid matrices can be explored to produce biosensors for detecting polyphenols, which is relevant for the food industry. Herein, we shall demonstrate the importance of the lipid composition to immobilize the enzyme tyrosinase in Langmuir-Blodgett (LB) films. Tyr could be incorporated into Langmuir monolayers of arachidic acid (AA), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dipalmitoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (sodium salt) (DPPG), having as the main effect an expansion in the monolayers. Results from polarization-modulated infrared reflection-absorption spectroscopy (PM-IRRAS) pointed to electrostatic interactions between the charged residues of Try and the lipid headgroups, in addition to changes in the order of lipid chains. The interaction between Tyr and DPPC in Langmuir monolayers can be correlated with the superior performance of DPPC/Tyr LB films used as biosensors to detect catechol by cyclic voltammetry. The molecular-level interactions assessed via PM-IRRAS are therefore believed to drive an immobilization process for Tyr in the lipid LB matrix and may serve as a general criterion to identify matrices that preserve enzyme activity.

A sandwich-type electrochemical immunosensor based on Au-rGO composite for CA15-3 tumor marker detection.

A sensitive detection of carbohydrate antigen 15-3 (CA15-3) levels may allow for early diagnosis and monitoring the treatment of breast cancer, but this can only be made in routine clinical practice if low-cost immunosensors are available. In this work, we developed a sandwich-type electrochemical immunosensor capable of rapid detection of CA15-3 with an ultra-low limit of detection (LOD) of 0.08 fg mL-1 within a wide linear concentration range from 0.1 fg mL-1 to 1 µg mL-1. The immunosensor had a matrix of a layer-by-layer film of Au nanoparticles and reduced graphene oxide (Au-rGO) co-electrodeposited on screen-printed carbon electrodes (SPCE). The high sensitivity was achieved by using secondary antibodies (Ab2) labeled with horseradish peroxidase (HRP) in the presence of hydrogen peroxide (H2O2) as signal amplifiers, and hydroquinone (HQ) was used as an electron mediator. The immunosensor was selective for CA15-3 in human serum and artificial saliva samples, robust, and stable to permit storage at 4 °C for more than 30 days. With its high performance, the immunosensor may be incorporated into future point-of-care (POC) devices to determine CA15-3 in distinct biological fluids, including in blood and saliva samples.

Flexible and integrated dual carbon sensor for multiplexed detection of nonylphenol and paroxetine in tap water samples.

Multiplex detection of emerging pollutants is essential to improve quality control of water treatment plants, which requires portable systems capable of real-time monitoring. In this paper we describe a flexible, dual electrochemical sensing device that detects nonylphenol and paroxetine in tap water samples. The platform contains two voltammetric sensors, with different working electrodes that were either pretreated or functionalized. Each working electrode was judiciously tailored to cover the concentration range of interest for nonylphenol and paroxetine, and square wave voltammetry was used for detection. An electrochemical pretreatment with sulfuric acid on the printed electrode enabled a selective detection of nonylphenol in 1.0-10 × 10-6 mol L-1 range with a limit of detection of 8.0 × 10-7 mol L-1. Paroxetine was detected in the same range with a limit of detection of 6.7 × 10-7 mol L-1 using the printed electrode coated with a layer of carbon spherical shells. Simultaneous detection of the two analytes was achieved in tap water samples within 1 min, with no fouling and no interference effects. The long-term monitoring capability of the dual sensor was demonstrated in phosphate buffer for 45 days. This performance is statistically equivalent to that of high-performance liquid chromatography (HPLC) for water analysis. The dual-sensor platform is generic and may be extended to other water pollutants and clinical biomarkers in real-time monitoring of the environment and health conditions. Silver pseudo-reference electrodes for paroxetine (REP) and nonylphenol (REN), working electrodes for paroxetine (WP) and nonylphenol (WN), and auxiliary electrode (AE). USP refers to the University of Sao Paulo. "Red" is reduced form and "Oxi" is oxidized form of analytes.

Chiral Dielectric Metasurfaces for Highly Integrated, Broadband Circularly Polarized Antenna.

We report on the design of a low-profile integrated millimeter-wave antenna for efficient and broadband circularly polarized electromagnetic radiation. The designed antenna comprises a chiral dielectric metasurface built with a 2×2 arrangement of dielectric cylinders with slanted-slots at the center. A broadbeam high-gain with wide axial ratio (AR)<3 dB bandwidth was reached by pairing the electric and magnetic resonances of the dielectric cylinders and the slanted slots when excited by an elliptically polarized driven-patch antenna. This electric-magnetic pairing can be tuned by varying the cylinders diameter and the tilting and rotation angles of the slanted slots. The simulation results indicate impedance-matching bandwidths up to 22.6% (25.3-31.6 GHz) with 3-dB AR bandwidths of 11.6% (26.9-30.2 GHz), which in terms of compactness (0.95λ0×0.95λ0) and performance are superior to previous antenna designs. Since the simulations were performed by assuming materials and geometries easily implementable experimentally, it is hoped that circularly polarized antennas based on chiral metasurfaces can be integrated into 5G and satellite communications.

In Vivo and In Vitro Taste Assessment of Artesunate-Mefloquine, Praziquantel, and Benznidazole Drugs for Neglected Tropical Diseases and Pediatric Patients.

The assessment of drug taste is crucial for pediatric treatments so that formulations can be developed to enhance their effectiveness. In this study, in vivo and in vitro methods were applied to evaluate the taste of tablets of three drugs administered to children without taste-masking excipients to treat tropical diseases, namely artesunate-mefloquine (ASMQ), praziquantel (PZQ), and benznidazole (BNZ). In the first method, a model of rat palatability was adapted with recirculation to ensure sample dispersion, and the data were analyzed using ANOVA (single factor, 95%). The taste assessment results (in vivo) indicated an aversion to the three medicines, denoted by the animals retracting themselves to the bottom of the box after the first contact with the drugs. For the placebo samples, the animals behaved normally, indicating that taste perception was acceptable. The second method was based on the in vitro analysis of capacitance data from a homemade impedimetric electronic tongue. Consistent with the in vivo taste assessment results, the data points obtained with PZQ, ASMQ, and BNZ were far away from those of their placebos in a map built with the multidimensional projection technique referred to as Interactive Document Mapping (IDMAP). A combined analysis of the results with the two methods allowed us to confirm the bitterness of the three drugs, also pointing to electronic tongues as a promising tool to replace in vivo palatability tests.

Chain Cleavage of Bioinspired Bacterial Membranes Photoinduced by Eosin Decyl Ester.

Photodynamic therapy (PDT) is promising for bacterial inactivation since cellular internalization of photosensitizers (PS) is not crucial for the treatment effectiveness. Photoinduced damage in the lipid envelope may already induce microbial inactivation, which requires PS capable of easily penetrating into the membrane. Herein, we report on the insertion of the PS eosin decyl ester (EosDec) into Langmuir films of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), 1,2-dioleoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (DOPG), and cardiolipin (CLP) used as mimetic systems of bacterial membranes. Surface pressure isotherms and polarization-modulated infrared reflection absorption spectroscopy (PM-IRRAS) indicated that the hydrophobic nature of EosDec favored deeper penetration in all the phospholipid monolayers. The incorporation of EosDec led to monolayer expansion, especially in the anionic DOPG and CLP owing to repulsive electrostatic interactions, and induced disorder in the lipid chains. Light irradiation of DOPE, DOPG, and CLP monolayers containing EosDec increased the rate of material loss to the subphase, which is attributed to cleavage of lipid chains triggered by contact-dependent reactions between excited states of EosDec and lipid unsaturations. The latter is key for membrane permeabilization and efficiency in microbial inactivation.

Controlled molecular architectures in microfluidic immunosensors for detecting Staphylococcus aureus.

Detection of pathogenic microorganisms is essential for food quality control and diagnosis of various diseases, which is currently performed with high-cost, sophisticated methods. In this paper, we report on a low-cost detection method based on impedance spectroscopy to detect Staphylococcus aureus (S. aureus). The immunosensors were made with microfluidic devices made of interdigitated electrodes coated with layer-by-layer (LbL) films of chitosan and chondroitin sulfate, on which a layer of anti-S. aureus antibodies was adsorbed. The limit of detection was 2.83 CFU mL-1 with a limit of quantification of 9.42 CFU mL-1 for immunosensors with 10-bilayer LbL films. This level of sensitivity is sufficient to detect traces of bacteria that cause mastitis in milk, which we have confirmed by distinguishing milk samples containing various concentrations of S. aureus from pure milk and milk contaminated with Escherichia coli (E. coli) and Salmonella. Distinction of these samples was made possible by projecting the electrical impedance data with the interactive document mapping (IDMAP) technique. The high sensitivity and selectivity are attributed to the highly specific interaction with anti-S. aureus antibodies captured with polarization-modulated reflection absorption spectroscopy (PM-IRRAS), with adsorption on the antibodies explained with the Langmuir-Freundlich model. Since these immunosensors are stable for up to 25 days and detection measurements can be made within minutes, the methodology proposed is promising for monitoring S. aureus contamination in the food industry and hospitals, and in detecting bovine mastitis.

Plasmonic Biosensing.

Plasmonic biosensing has been used for fast, real-time, and label-free probing of biologically relevant analytes, where the main challenges are to detect small molecules at ultralow concentrations and produce compact devices for point-of-care (PoC) analysis. This review discusses the most recent, or even emerging, trends in plasmonic biosensing, with novel platforms which exploit unique physicochemical properties and versatility of new materials. In addition to the well-established use of localized surface plasmon resonance (LSPR), three major areas have been identified in these new trends: chiral plasmonics, magnetoplasmonics, and quantum plasmonics. In describing the recent advances, emphasis is placed on the design and manufacture of portable devices working with low loss in different frequency ranges, from the infrared to the visible.

Refractive index of ZnO ultrathin films alternated with Al2O3 in multilayer heterostructures.

The design of optoelectronic devices made with ZnO superlattices requires the knowledge of the refractive index, which currently can be done only for films thicker than 30 nm. In this work, we present an effective medium approach to determine the refractive index of ZnO layers as thin as 2 nm. The approach was implemented by determining the refractive index of ZnO layers ranging from 2 nm to 20 nm using spectroscopic ellipsometry measurements in multilayers. For a precise control of morphology and thickness, the superlattices were fabricated with atomic layer deposition (ALD) with alternating layers of 2 nm thick Al2O3 and ZnO, labeled as N ZnO-Al2O3, where N = 10, 20, 30, 50, 75 and 100. The total thickness of all superlattices was kept at 100 nm. The approach was validated by applying it to similar superlattices reported in the literature and fitting the transmittance spectra of the superlattices.

Decoupling Temperature-Volume Effects on Poly[2-Methoxy-5-(2'-Ethylhexyloxy)-1,4-Phenylene-Vinylene] Films at the ß-Relaxation Temperature.

In this paper, we report a simple procedure to decouple effects from temperature and volume on the emission properties of thin films of poly[2-methoxy-5-(2'-ethylhexyloxy)-1,4-phenylene-vinylene] (MEH-PPV). This procedure consists of applying a positive pressure close to the ß-relaxation temperature, Tß (∼220 K), of MEH-PPV, which controls the molecular movement to retain a disordered state for the polymer chains even after the sample is cooled from room temperature. Such decoupling could be confirmed by calculating the photoluminescence (PL) spectra line shape using a semi-empirical model based on molecular exciton and Franck-Condon transitions, and with electron-vibrational modes coupling being parameterized with the Huang-Rhys factor. We also show that the decoupling between temperature and volume effects does not occur if the molecular movement is restricted either by thermal annealing or by depositing the MEH-PPV film on a rigid substrate. This latter finding may be exploited in designing thermally stable devices.

Determination of p53 biomarker using an electrochemical immunoassay based on layer-by-layer films with NiFe2O4 nanoparticles.

A disposable electrochemical immunosensors is presented suitable to detect cancer biomarker p53 using screen-printed carbon electrodes modified with a layer-by-layer (LbL) matrix of carboxylated NiFe2O4 nanoparticles and polyethyleneimine, onto which anti-p53 antibodies were adsorbed. Under optimized conditions, the immunosensors exhibited high surface coverage and high concentration of immobilized antibodies, which allowed for detection of p53 in a wide dynamic range from 1.0 to 10 × 103 pg mL-1, with a limit of detection of 5.0 fg mL-1 at a working potential of 100 mV vs. Ag/AgCl. The immunosensors also exhibited good selectivity with negligible interference upon incubation in complex matrices containing high concentrations of proteins (i.e., fetal bovine serum and cell lysate). The immunosensor performance is among the best reported in the literature for determination of p53, with the additional advantage of being disposable and operating with low-volume solutions.Graphical abstract Schematic representation of immunosensor fabrication depicting the immobilization of specific antibodies against p53 protein onto the surfaces of disposable printed electrodes modified with films of polyethyleneimine and different concentrations of carboxylated magnetic nanoparticles.