We developed a surface-enhanced Raman scattering (SERS)-active plasmonic core-satellite nanostructure and incorporated it into a membrane filter-integrated microfluidic device for continuous monitoring of molecules in solution. The core-satellite nanostructures were fabricated by immobilizing a high number density of gold nanoparticles (AuNPs) on silica beads.to create many nanogaps among the AuNPs. The sizes of the nanogaps were fine-tuned by adding a silver (Ag) shell to optimize the SERS activity. In addition, citrate molecule, the capping agent of the nanoparticles, was displaced by alkali halides. The displacement not only reduced the SERS signals of citrate but also enhanced the adsorption of target molecules. The alkali halide-treated core-satellite nanostructures were accumulated onto a membrane filter integrated into a microfluidic device, serving as a uniform and sensitive SERS substrate. By increasing the volume of the sample solution flowing through the membrane filter, we increased the number of molecules adsorbed to the nanostructures, amplifying the intensities of their characteristic Raman peaks. Our microfluidic SERS device demonstrated continuous SERS detection of malachite green at a concentration as low as 500 fM. In summary, while various core-satellite nanostructures and microfluidic SERS devices have been reported, the integration of the membrane filter-containing microfluidic device with the core-satellite nanostructures facilitated sensitive and continuous molecule detection in our study.

Surface-enhanced Raman scattering (SERS) is a highly sensitive technique used in diverse biomedical applications including rapid antibiotic susceptibility testing (AST). However, signal fluctuation in SERS, particularly the widespread of signals measured from different batches of SERS substrates, compromises its reliability and introduces potential errors in SERS-AST. In this study, we investigate the use of purine as an internal standard (IS) to recalibrate SERS signals and quantify the concentrations of two important purine derivatives, adenine and hypoxanthine, which are the most important biomarkers used in SERS-AST. Our findings demonstrate that purine IS effectively mitigates SERS signal fluctuations and enables accurate prediction of adenine and hypoxanthine concentrations across a wide range (5 orders of magnitude). Calibrations with purine as an IS outperform those without, exhibiting a 10-fold increase in predictive accuracy. Additionally, the calibration curve obtained from the first batch of SERS substrates remains effective for 64 additional substrates fabricated over a half-year period. Measurements of adenine and hypoxanthine concentrations in bacterial supernatants using SERS with purine IS closely align with the liquid chromatography–mass spectrometry results. The use of purine as an IS offers a simple and robust platform to enhance the speed and accuracy of SERS-AST, while also paving the way for in situ SERS quantification of purine derivatives released by bacteria under various stress conditions.

Bloodstream infections are a growing public health concern due to emerging pathogens and increasing antimicrobial resistance. Rapid antibiotic susceptibility testing (AST) is urgently needed for timely and optimized choice of antibiotics, but current methods require days to obtain results. Here, we present a general AST protocol based on surface-enhanced Raman scattering (SERS-AST) for bacteremia caused by eight clinically relevant Gram-positive and Gram-negative pathogens treated with seven commonly administered antibiotics. Our results show that the SERS-AST protocol achieves a high level of agreement (96% for Gram-positive and 97% for Gram-negative bacteria) with the widely deployed VITEK 2 diagnostic system. The protocol requires only five hours to complete per blood-culture sample, making it a rapid and effective alternative to conventional methods. Our findings provide a solid foundation for the SERS-AST protocol as a promising approach to optimize the choice of antibiotics for specific bacteremia patients. This novel protocol has the potential to improve patient outcomes and reduce the spread of antibiotic resistance.

A physical mechanism to produce pulsating aurora (PsA) has been considered to be the interaction of the electron and the chorus wave generated near the equatorial plane of the magnetosphere. A recent observation of high temporal resolution of chorus waves by the Arase satellite revealed that the presence or absence of the internal modulation of PsA, which is a characteristic sub‐second scintillation at 3 ± 1 Hz within each optical pulsation, is closely related to the discreteness of the element structure of the chorus wave. However, it is still unclear what parameters (or conditions) control the discreteness of the element and the existence of the internal modulation of PsA. In this study, we discuss parameters that determine the presence or absence of the internal modulation of PsA and element structure of chorus by showing a conjugate observation of PsA/chorus by ground‐based cameras and the Arase satellite. During the event, the occurrence of internal modulation increased temporally. The wave data from the satellite show that the repetitive frequency of elements was ∼6 Hz when the internal modulation was indistinct, while the repetitive frequency was ∼3 Hz when the internal modulation was distinct. The particle measurements suggest that this difference was caused by changes in the density and the temperature anisotropy of the hot electron. The internal modulation was clearly observed when the density of hot electrons decreased and the temperature anisotropy relaxed after the injection. Observations of internal modulations from the ground might allow us to estimate the parameters such as energetic electron density and temperature anisotropy in the magnetosphere.

Electronic cigarettes have rapidly gained acceptance recently. Nicotine-containing electronic cigarette liquids (eliquids) are prohibited in some countries, but are permitted and simply available online in others. A rapid detection method is therefore required for on-site inspection or screening of a large amount of samples. Our previous study demonstrated a surface-enhanced Raman scattering (SERS)-based approach to identify nicotinecontaining e-liquids; without any pre-treatment, e-liquid can be directly tested on our solid-phase SERS substrates, made of silver nanoparticle arrays embedded in anodic aluminium oxide nanochannels (Ag/AAO). However, this approach required manual determination of spectral signatures and negative samples should be validated in the second round detection. Here, after examining 406 commercial e-liquids, we refined this approach by developing artificial intelligence (AI)-assisted spectrum interpretations. We also found that nicotine and benzoic acid can be simultaneously detected in our platform. This increased test sensitivity because benzoic acid is usually used in nicotine salts. Around 64% of nicotine-positive samples in this study showed both signatures. Using either cutoffs of nicotine and benzoic acid peak intensities or a machine learning model based on the CatBoost algorithm, over 90% of tested samples can be correctly discriminated with only one round of SERS measurement. False negative and false positive rates were 2.5-4.4% and 4.4-8.9%, respectively, depending on the interpretation method and thresholds applied. The new approach takes only 1 microliter of sample and can be performed in 1-2 min, suitable for on-site inspection with portable Raman detectors. It could also be a complementary platform to reduce samples that need to be analyzed in the central labs and has the potential to identify other prohibited additives.

Antimicrobial susceptibility testing (AST) is a key measure in clinical microbiology laboratories to enable appropriate antimicrobial administration. During an AST, the determination of the minimum inhibitory concentration (MIC) is an important step in which the bacterial responses to an antibiotic at a series of concentrations obtained in separate bacterial growth chambers or sites are compared. However, the preparation of different antibiotic concentrations is time-consuming and labor-intensive. In this paper, we present a microfluidic device that generates a concentration gradient for antibiotics that is produced by diffusion in the laminar flow regime along a series of lateral microwells to encapsulate bacteria for antibiotic treatment. All the AST preparation steps (including bacterium loading, antibiotic concentration generation, buffer washing, and isolated bacterial growth with an antibiotic) can be performed in a single chip. The viable bacterial cells in each microwell after the antibiotic treatment are then quantified by their surface-enhanced Raman scattering (SERS) signals that are acquired after placing a uniform SERS-active substrate in contact with all the microwells. For proof-of-concept, we demonstrated the AST performance of this system on ampicillin (AMP)-susceptible and -resistant E. coli strains. Compared with the parameters for conventional AST methods, the AST procedure based on this chip requires only 20 μL of bacteria solution and 5 h of operation time. This result indicates that this integrated system can greatly shorten and simplify the tedious and labor-intensive procedures required for current standard AST methods.

Temperature sensing is a promising method of enhancing the detection sensitivity of lateral flow immunoassay (LFIA) for point-of-care testing. A temperature increase of more than 100 °C can be readily achieved by photoexcitation of reporters like gold nanoparticles (GNPs) or colored latex beads (CLBs) on LFIA strips with a laser power below 100 mW. Despite its promise, processes involved in the photothermal detection have not yet been well-characterized. Here, we provide a fundamental understanding of this thermometric assay using non-fluorescent CLBs as the reporters deposited on nitrocellulose membrane. From a measurement for the dependence of temperature rises on the number density of membrane-bound CLBs, we found a 1.3-fold (and 3.2-fold) enhancement of the light absorption by red (and black) latex beads at 520 nm. The enhancement was attributed to the multiple scattering of light in this highly porous medium, a mechanism that could make a significant impact on the sensitivity improvement of LFIA. The limit of detection was measured to be 1 × 105 particles/mm2. In line with previous studies using GNPs as the reporters, the CLB-based thermometric assay provides a 10× higher sensitivity than color visualization. We demonstrated a practical use of this thermometric immunoassay with rapid antigen tests for COVID-19.

Lateral flow immunoassay (LFIA) is a widely used tool for point-of-care testing (POCT). Although the method is fast and inexpensive, it provides only qualitative or semi-quantitative information, which limits the scope of its applications in POCT. Here, we report the development of a low-cost, portable LFIA reader based on photothermal detection of reporters (such as colloidal gold and colored latex beads) captured on LFIA strips using a low-power green laser as the heating source and a single-element infrared sensor as the detector. For 40-nm colloidal gold, we measured a detection limit of 3 x 10(5) particles/mm(2) by laser irradiation of the reporters at 532 nm with an intensity of 20 W/cm(2). The photothermal detection enables a 10-fold enhancement in sensitivity over color visualization with the naked eye. More importantly, with the use of the control line intensities as internal calibrants, the results so obtained are quantitative and useful to support critical decision-making in POCT, as demonstrated by gold-based assays for human chorionic gonadotropin and human immunodeficiency virus as well as latex-based assays for nucleocapsid protein of the SARS-CoV-2 virus.

Abstract Background As effective management of sepsis requires timely administration of appropriate antibiotics, a reliable and rapid antimicrobial susceptibility testing (AST) is crucial. To meet clinical needs, we developed a novel AST, referred to as SERS-AST, based on the surface-enhanced Raman Scattering (SERS) technology. SERS-AST determines antibiotic susceptibility of bacteria based on variations in bacterial SERS signals derived from secreted purines and their derivatives. Methods SERS-AST was applied to blood culture samples of patients with bacteremia. Eight common causative organisms, including Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Enterococcus faecium, Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae, and Acinetobacter baumannii and seven most prescribed antibiotics, including oxacillin, levofloxacin, vancomycin, ampicillin, cefotaxime, ceftazidime, levofloxacin, and imipenem were tested. Receiver operating characteristic analysis was performed to obtain the optimal cutoff SERS signal value to determine the susceptibility of tested bacteria. The results of SERS-AST were compared with those of VITEK 2. Results A total of 164 bacterial isolates from blood samples were examined, and the agreement rates between SERS-AST and VITEK 2 results were 96% for Gram-positive bacteria and 97% for Gram-negative bacteria. Conclusions By directly assaying positive blood cultures without additional subcultures, SERS-AST can be completed within 4 hours with high accuracy. It can be an alternative AST method to provide critical information to clinicians for timely administration of appropriate antibiotics to treat patients with blood stream infections.

A new flexible, super-hydrophobic, and highly sensitive polydimethylsiloxane (PDMS) based-substrate would be developed for surface-enhanced Raman spectroscopy (SERS) detection. PDMS substrate is modified by nitrogen plasma and then deposited the organic conjugated molecules (alpha, omega-diperfluorohexylquaterthiophene, DFH-4T) films various thickness of Au nanoislands. The perfluorohexyl (-n-C6F13) chain of DFH-4T displays the advantages of high volatility and low vapor deposition temperature and can form a super-hydrophobic ivy-like nanostructure. After depositing the Au nanoislands on DFH-4T, the vertically arranged Au-DFH-4T nanostructure combined provides a tip-focusing effect and generates a very high electromagnetic field to enhance the Raman signal. Benefiting from the hydrophobic ivy-like nanostructure (maximum contact angle: similar to 146(o)) of Au@DFH-4T nanostructure, the hydrophobic molecule (vitamin D3, cholecalciferol) can be measured at ultralow concentration (10(-10) M). Moreover, the flexible SERS sensor exhibited acceptable efficiency and durability after 100 cycles bending tests. SERS intensity would increase similar to 1.6 time at 0.35 cm bending radius. This facile and efficient detection technique for meeting the increased demands for bio-detection, especially for hydrophobic biomolecules.

Effective management of sepsis requires timely administration of appropriate antibiotics; therefore, a reliable and rapid antimicrobial susceptibility test (AST) is crucial. To meet clinical needs, we developed a novel AST, referred to as SERS-AST, based on the surface-enhanced Raman Scattering (SERS) technology. In this study, we applied SERS-AST to eight most common pathogens causing bacteremia, including Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, E. faecium, Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae , and Acinetobacter baumannii . Seven different antibiotics were tested, including oxacillin, levofloxacin, vancomycin, ampicillin, cefotaxime, ceftazidime, levofloxacin, and imipenem. SERS-AST determines antibiotic susceptibility of bacteria directly from positive blood cultures based on variations in bacterial SERS signals derived from secreted purines and their derivatives. The whole process could be completed within 4 hours, and the agreement rates between SERS-AST and VITEK 2 results were 96% for Gram-positive bacteria and 97% for Gram-negative bacteria.

High-temperature superconductive (SC) cuprates exhibit not only a SC phase, but also competing orders, suppressing superconductivity. Charge order (CO) has been recognized as an important competing order, but its microscopic spatial interplay with SC phase as well as the interlayer coupling in CO and SC phases remain elusive, despite being essential for understanding the physical mechanisms of competing orders and hence superconductivity. Here we report the achievement of direct real-space imaging with atomic-scale resolution of cryogenically cleaved YBa 2 Cu 3 O 6.81 using cross-sectional scanning tunneling microscopy/spectroscopy. CO nanodomains are found embedded in the SC phase with a proximity-like boundary region characterized by mutual suppression of CO and superconductivity. Furthermore, SC coherence as well as CO occur on both CuO chain and plane layers, revealing carrier transport and density of states mixing between layers. The CO antiphase correlation along the c direction suggests a dominance of Coulomb repulsion over Josephson tunneling between adjacent layers.

Temperature sensing is a promising method of enhancing the detection sensitivity of lateral flow immunoassay for point-of-care testing. A temperature increase of more than 100 °C can be readily achieved by photoexcitation of reporters like gold nanoparticles (GNPs) or colored latex beads (CLBs) on the strips with a laser power below 100 mW. Despite its promise, processes involved in the photothermal detection have not yet been well-characterized. Here, we provide a fundamental understanding of this thermometric assay by combining experiments and simulations using non-fluorescent CLBs as the reporters deposited on nitrocellulose membrane. By measuring the dependence of temperature rises on the number density of membrane-bound CLBs, we determined a 1.5-fold enhancement of the light absorption at 520 nm by the beads (diameter of 0.4 μm). The enhancement, however, was compromised by a 5-fold reduction of the incident laser power due to multiple scattering of the light in this highly porous medium. The limit of detection was measured to be 1 × 10 5 particles/mm 2 . In line with previous studies using GNPs as the reporters, the CLB-based thermometric assay provides a 10× higher sensitivity than color visualization, as demonstrated with the immunoassay for nucleocapsid proteins of the SARS-CoV-2 virus.

Identifying and quantifying chromium in water are important for the protection of precious water resources from chromium pollution. Standard methods however are unable to easily distinguish toxic hexavalent chromium, Cr(VI), from innocuous trivalent chromium, Cr(III), are time-consuming, or require large sample quantity. We show in this report that Cr(VI) and Cr(III) in water can be differentiated based on their distinct spectral features of surface-enhanced Raman scattering (SERS). Their SERS signals exhibit different pH dependences: the SERS features of Cr(VI) and Cr(III) are most prominent at pH values of 10 and 5.5, respectively. The obtained limit of detection of Cr(VI) in water is below 0.1 mg/L. Both concentration curves of their SERS signals show Langmuir sorption isotherm behavior. A procedure was developed to quantify Cr(VI) concentration based on the direct retrieval or addition method with an error of 10%. Finally, the SERS detection of Cr(VI) is shown to be insensitive to co-present Cr(III). The developed SERS procedure offers potential to monitor toxic chromium in fields.

We developed a method based on surface-enhanced Raman spectroscopy (SERS) and a sample pretreatment process for rapid, sensitive, reproducible, multiplexed, and low-cost detection of illegal drugs in urine. The abuse of new psychoactive substances (NPS) has become an increasingly serious problem in many countries. However, immunoassay-based screening kits for NPS are usually not available because of the lack of corresponding antibodies. SERS has a great potential for rapid detection of NPS because it can simultaneously detect multiple kinds of drugs without the use of antibodies. To achieve highly sensitive SERS detection of drugs, sodium bromide was first employed to induce the rapid formation of Ag nanoclusters by aggregating silver nanoparticles (AgNPs) in the extracted sample solution. SERS measurements were performed immediately after the sample pretreatment without incubation. The three-dimensional SERS hot spots were believed to form significantly within the nanoclusters, providing strong SERS enhancement effects. The displacement of citrate molecules on the surfaces of the AgNPs by bromide ions helped increase the adsorption of drug molecules, increasing their areal density. We demonstrated the simultaneous detection of two kinds of NPS, methcathinone and 4-methylmethcathinone, in urine at a concentration as low as 0.01 ppm.

Bloodstream infection (BSI) is a serious public health issue worldwide. Timely and effective antibiotics for controlling infection are crucial towards patient outcomes. However, the current culture-based methods of identifying bacteria and antimicrobial susceptibility testing (AST) remain labor-intensive and time-consuming, and are unable to provide early support to physicians in critical hours. To improve the effectiveness of early antibiotic therapy, Surface-enhanced Raman scattering (SERS) technology, has been used in bacterial detection and AST based on its high specificity and label-free features. To simplify sample preparation steps in SERS-AST, we proposed an automated microfluidic control system to integrate all required procedures into a single device. Our preliminary results demonstrated the system can achieve on-chip reagent replacement, bacteria trapping, and buffer exchange. Finally, in-situ SERS-AST was performed within 3.5 h by loading isolates of ampicilin susceptible and resistant E. coli and clear discrimination of two strains under antibiotic treatment was demonstrated. Overall, our system can standardize and simplify the SERS-AST protocol and implicate parallel bacterial detection. This prototypical integration demonstrates timely microbiological support to optimize early antibiotic therapy for fighting bacteremia.

Silver nanoparticles grown in nanochannels of anodic aluminum oxide on a grating form a surface-enhanced Raman scattering (SERS) substrate with the double resonance from both localized and delocalized plasmons. With angle-resolved reflectance spectroscopy, we characterized the propensity of surface plasmon polariton (SPP) of the grating and confirmed it with electrodynamic simulation. In addition to the hot spots created between adjacent silver nanoparticles, the extra SERS enhancement engendered by the grating's SPP manifested as the enhancement band over a range of detection angles. The SERS signal of thiophenol obtained with transverse-magnetic excitation showed a gain by a factor of 2, which is comparable with the one estimated from local-field simulation. The electrodynamic simulation showed that the most normally directed local field at the surface may limit the field enhancement of localized plasmonic coupling between silver nanoparticles. With the incorporation of grating, the enhanced SERS signals are inherently wavelength-dispersed, thus enabling simpler designs of SERS-based sensors without a spectrometer.