Variable-Angle Surface Spectroscopy Reveals the Water Structure in the Stern Layer at Charged Aqueous Interfaces.

At charged aqueous interfaces, the second-order nonlinear optical response originates from water molecules within the diffuse part of the electrical double layer, which are ordered by the surface field and from water that additionally experiences chemical and physical interactions with the surface in the Stern layer. These two environments can either reinforce or diminish the overall signal and can be disentangled by varying the coherence length of their interaction with external laser fields. Here, we demonstrate a method in which the angle of incidence is varied to afford a significant change in the coherence length. When this technique was applied to the silica-water interface, it was observed that water molecules in the Stern and diffuse layers direct their hydrogen atoms toward the mineral surface at a low ionic strength and neutral pH. A decrease in the signal with increasing ionic strength is attributed to hydrated cation adsorption that competes with free water for deprotonated silanol sites.

Surface Structural Changes in Silicone Rubber Due to Electrical Tracking.

There is a growing interest in the use of silicone composite insulators for electrical power transmission and distribution applications. However, such materials are susceptible to degradation as they are exposed to electrical and environmental stresses during operating conditions. Therefore, it is crucial to gain a thorough understanding of the degradation mechanism through changes in the material structure that may provide insight into potential failures in the electrical grid. Attenuated total reflection Fourier transform infrared spectroscopy and two-dimensional correlation spectroscopy (2D-COS) were used along with contact angle measurements to characterize changes in silicone rubber samples from actual insulators subjected to tracking wheel testing. The results showed a decrease in absorbance of different infrared bands representing different functional groups, such as Si-O-Si, methyl functional groups, and both Al-O and hydroxyl groups of alumina trihydrate as a function of the number of tracking cycles. The sequence of changes in the functional groups was determined by 2D-COS as Al-O and OH followed by Si-O-Si polymer backbone modes, followed by polymer methyl side chains. An enhancement in the average contact angle with the number of tracking cycles revealed a concomitant increase in surface roughness with electrical tracking.

Development of a neural network model to predict the presence of fentanyl in community drug samples.

INTRODUCTION: Increasingly, Fourier-transform infrared (FTIR) spectroscopy is being used as a harm reduction tool to provide people who use drugs real-time information about the contents of their substances. However, FTIR spectroscopy has been shown to have a high detection limit for fentanyl and interpretation of results by a technician can be subjective. This poses concern, given that some synthetic opioids can produce serious toxicity at sub-detectable levels. The objective of this study was to develop a neural network model to identify fentanyl and related analogues more accurately in drug samples compared to traditional analysis by technicians. METHODS: Data were drawn from samples analyzed point-of-care using combination FTIR spectroscopy and fentanyl immunoassay strips in British Columbia between August 2018 and January 2021. We developed neural network models to predict the presence of fentanyl based on FTIR data. The final model was validated against the results from immunoassay strips. Prediction performance was assessed using F1 score, accuracy, and area under the receiver-operating characteristic curve (AUROC), and was compared to results obtained from analysis by technicians. RESULTS: A total of 12,684 samples were included. The neural network model outperformed results from those analyzed by technicians, with an F1 score of 96.4% and an accuracy of 96.4%, compared to 78.4% and 82.4% with a technician, respectively. The AUROC of the model was 99.0%. Fentanyl positive samples correctly detected by the model but not by the technician were typically those with low fentanyl concentrations (median: 2.3% quantity by weight; quartile 1-3: 0.0%-4.6%). DISCUSSION: Neural network models can accurately predict the presence of fentanyl and related analogues using FTIR data, including samples with low fentanyl concentrations. Integrating this tool within drug checking services utilizing FTIR spectroscopy has the potential to improve decision making to reduce the risk of overdose and other negative health outcomes.

Second-Order Nonlinear Optics as an Orientation-Independent Probe of Molecular Environments at Interfaces.

Measurement techniques that probe the second-order susceptibility, such as second-harmonic and sum-frequency generation, are recognized for their ability to study environments with broken centrosymmetry. As a result, they serve as reporters of molecules at surfaces because the second-order susceptibility is often zero in the adjacent bulk media. Although the signals measured in such experiments carry unique information about the interfacial environment, the challenge is to disentangle properties related to the electronic structure as they are wrapped up in the orientation distribution. Over the past 30 years, this challenge has been turned into an opportunity, as many studies have sought to learn about the arrangement of molecules at surfaces. Here we demonstrate that the flipped case is possible, where fundamental properties of the interfacial environment can be extracted in a manner that is completely independent of, and therefore oblivious to, the orientation distribution. Using p-cyanophenol adsorbed at the air-water interface as an example, we illustrate that the cyano group polarizability varies less along the direction of the C-N bond when at the surface than when the same molecules are in the bulk aqueous phase.

Carfentanil structural analogs found in street drugs by paper spray mass spectrometry and their characterization by high-resolution mass spectrometry.

Carfentanil is one of the most potent synthetic opioids ever developed, with an estimated analgesic potency approximately 20-100 times that of fentanyl and 10,000 times that of morphine. Carfentanil has been appearing in the illicit drug supply in many regions and has been linked to fatal overdose events. A subset of 59 street drug samples obtained in Victoria, B.C., that were confirmed to contain carfentanil were analyzed by mass spectrometry for this study. Carfentanil quantitation by paper spray mass spectrometry ranged from 0.05 to 2.95 w/w% (median = 0.32%) in the original drug sample. Paper spray mass spectrometry analysis also detected two unknown peaks at m/z 380.2 and 381.2 in 31 of these 59 samples (53%). Initial tandem mass spectrometry experiments revealed structural similarities between these unknown compounds and carfentanil, suggesting they were potential structural analogs, possibly arising from incomplete purification during synthesis. High-resolution mass spectrometry determined the chemical formulas of these compounds as C23 H29 N3 O2 (m/z 380.2333) and C23 H29 N2 O3 (m/z 381.2137). Literature and tandem mass spectrometry results were used to determine the identity of these potential new psychoactive substances, C23 H29 N3 O2 as desmethylcarfentanil amide and C23 H29 N2 O3 as desmethylcarfentanil acid. µ-Opioid receptor binding modeling determined that the binding poses of these analogs were nearly identical to that of carfentanil with relative binding energy calculations of 0.544 kJ/mol (desmethylcarfentanil amide) and -0.171 kJ/mol (desmethylcarfentanil acid); these data suggest they may share the toxic effects of carfentanil and have similar potencies.

Vibrational sum frequency spectroscopy of thin film interfaces.

We describe a basic theoretical treatment of how film-substrate and substrate-environment (air, water, and solution) interfaces can be selectively probed by controlling the film thickness and beam angles in a visible-infrared sum frequency generation experiment. In this model, we also account for the unique interfacial environment that may have optical properties that differ from the adjacent bulk phases. We see that this affects components of the electric field that are perpendicular to the surface such as when p-polarized light is used. We then provide an example using the glass-polydimethylsiloxane-air system and model the fields at both surfaces of the polymer. This is followed by some practical considerations for setting up such experiments and some typical experimental results.

Ion Depletion in the Interfacial Microenvironment from Cell-Surface Interactions.

The nanoscale region immediately adjacent to surfaces, although challenging to probe, is directly responsible for local chemical and physical interactions between a material and its surroundings. Cell-surface contacts are mediated by a combination of electrostatic and acid-base interactions that alter the local environment over time. In this study, a label-free vibrational probe with a nanometer length scale reveals that the electrostatic potential at a silica surface gradually increases in the presence of bacteria in solution. We illustrate that the cells themselves are not responsible for this effect. Rather, they alter the interfacial chemical environment in a manner that is consistent with a reduction of the ionic strength to a level that is roughly four times lower than that of the bulk aqueous phase.

Temperature-Dependent Infrared Refractive Index of Polymers from a Calibrated Attenuated Total Reflection Infrared Measurement.

We demonstrate a straightforward method by which a commonly available reference sample such as water can be used to calibrate an attenuated total internal reflection infrared absorbance measurement in order to account for the polarization of the beam incident on the internal reflecting element, and the spread of angles about the nominal angle of incidence. This enables quantitative comparison of attenuated total reflection-derived absorbance data with spectra calculated from optical constants. We then apply this calibration to the measurement of temperature-dependent absorption spectra of a polydimethylsiloxane sample. We illustrate that the extracted optical constants scale with the temperature-dependent changes in the polymer density better than the raw absorbance values on vibrational resonance.

Rapid and accurate etizolam detection using surface-enhanced Raman spectroscopy for community drug checking.

BACKGROUND: In British Columbia, Canada, illicit opioids have been increasingly combined with etizolam, a benzodiazepine analog, that continues to challenge popular portable drug checking technologies as it is often present in low concentrations as a result of its high potency. An unknown combination of opioids and benzodiazepines may have dangerous consequences due to unpredictable dosing, increased respiratory depression, and complicated overdose response measures. METHODS: Surface-enhanced Raman spectroscopy (SERS) using a portable Raman spectrometer is used to establish a univariate model for the detection of etizolam in opioid drug mixtures (n=100) obtained from the Vancouver Island Drug Checking Project, where the presence of etizolam has been determined using paper-spray mass spectrometry. Benzodiazepine immunoassay test strips are also performed on all samples for comparison. RESULTS: SERS is shown to detect etizolam with high sensitivity (96%) and specificity (86%). In contrast, benzodiazepine test strips demonstrate a low sensitivity (8%) for the detection of etizolam of the same samples (n=100), with only small improvements when studied over a larger subset of samples (n=506, sensitivity = 29%). CONCLUSION: We have demonstrated the potential of SERS for trace detection of etizolam within complex sample matrices. Since SERS is one of the few portable technologies capable of trace detection, further studies on its ability for quantification and discrimination of trace adulterants in street samples is of significant interest for point-of-care applications.

Third party drug checking: accessing harm reduction services on the behalf of others.

BACKGROUND: Drug checking uses chemical analytical technologies to analyze drugs from the unregulated market to reduce substance use-related risks. We aim to examine the frequency of third party use of a community drug checking service to explore the potential for harm reduction to extend beyond the individual into the community, increase service accessibility, and to contribute to upstream interventions in the supply. METHODS: Over 31 months, data were collected from a point-of-care drug checking service operated in Victoria, Canada. Through the implementation of survey questions at the intake of the service, data were collected about whether the drug check was for the individual, to sell, and/or for others. RESULTS: Just over half (52%) of service users were checking for reasons that extended beyond individual use. When checking for others, friends were the most common response, representing 52% of responses, and outreach/support workers checking for others was the second most at 32%. Twelve percent of service users reported checking to sell or for a supplier. CONCLUSIONS: Third party checking is a frequent, and important aspect of drug checking services, which through facilitating community engagement and increasing accessibility, has expanded the reach of interventions beyond individuals to reduce risks within the unregulated market. Therefore, drug checking as an overdose response should be responsive and accessible for those using the service on the behalf of others.

Portable gas chromatography-mass spectrometry in drug checking: Detection of carfentanil and etizolam in expected opioid samples.

BACKGROUND: There has been a recent increase in adulteration of opioids with low concentration actives such as fentanyl analogues and benzodiazepines. As drug checking projects using vibrational spectroscopy continue to seek confirmatory lab-based testing, the concern and reality of missing these potentially harmful substances in point-of-care testing is prevalent. METHODS: A portable GC-MS was used to analyze select opioid samples acquired at a drug checking service in Victoria, Canada (n=59). Certified reference standards of several fentanyl analogues and benzodiazepines were measured to guide targeted analysis of these samples. Results were compared with those obtained using a lab-based paper spray mass spectrometer. RESULTS: Portable GC-MS was able to identify 62% of samples containing carfentanil and 36% of samples containing etizolam. In the case of etizolam, the success rate was higher for more potent samples: 78% of etizolam-containing samples were identified when the etizolam concentration was above 3% by weight. In comparison, infrared spectroscopy was able to detect etizolam in only 9% of the etizolam-containing samples, and is not sensitive enough to detect carfentanil at relevant concentrations. CONCLUSIONS: Portable GC-MS has potential in identifying low concentration substances in a point-of-care setting, without relying on subsequent off-site confirmatory testing.

All-experimental analysis of doubly resonant sum-frequency generation spectra: Application to aggregated rhodamine films.

A new method is proposed to analyze Doubly Resonant infrared-visible Sum-Frequency Generation (DR-SFG) spectra. Based on the transform technique, this approach is free from assumptions about vibronic modes, energies, or line widths and accurately captures through the overlap spectral function all required aspects of the vibronic structure from simple experimental linear absorption spectra. Details and implementation of the method are provided along with three examples treating rhodamine thin films about one monolayer thick. The technique leads to a perfect agreement between experiment and simulations of the visible DR-SFG line shapes, even in the case of complex intermolecular interactions resulting from J-aggregated chromophores in heterogeneous films. For films with mixed H- and J-aggregates, separation of their responses shows that the J-aggregate DR-SFG response is dominant. Our analysis also accounts for the unexplained results published in the early times of DR-SFG experiments.

Algae Adhesion onto Silicone is Sensitive to Environment-Induced Surface Restructuring.

Resistance to algae contamination is an important characteristic of insulators used in overhead power distribution in coastal environments. It is therefore important to understand the parameters governing algae adhesion onto polymer insulator materials such as silicone. Flow cell-based shear experiments were conducted in order to characterize the adhesion strength of algae onto polydimethylsiloxane surfaces, comparing fresh polymer substrates with those that have been soaked in water and saline solutions for 1 month. Both freshwater algae and seawater species could withstand considerably less drag force and were therefore more easily removed when the polymer was soaked in salt water. The polymer surface was found to be unaltered in terms of its roughness, contact angle, and lack of water uptake; no macroscopic surface characterization was therefore able to account for the differences in cell adhesion strength resulting from the soaking treatment. Surface-specific nonlinear vibrational spectroscopy, however, revealed subtle differences in the orientation of surface methyl groups that resulted from the water and saline exposure.

An automated image analysis platform for the study of weakly -adhered cells.

Details of the design and implementation of an open-source platform for studying the adhesion of cells attached to solid substrata are provided. The hardware is based on a laser-cut flow channel connected to a programmable syringe pump. The software automates all aspects of the flow rate profile, data acquisition and image analysis. An example of the pelagic diatom Thalassiosira rotula adhered to poly(dimethyl siloxane) surfaces is provided. The procedure described enables the shear rate to be converted to drag force for arbitrary-shaped objects, of utility to the study of many cell species, especially ones that are obviously non-spherical. It was determined that 90% of cells are removed with the application of drag forces < 3×10-12 N, and that this value is relatively independent of the incubation time on the surface. This result is important to understand how marine species interact with polymer surfaces that are used in electrical insulator applications.

Determining nonlinear optical coefficients of metals by multiple angle of incidence heterodyne-detected sum-frequency generation spectroscopy.

We illustrate a technique by which heterodyne-detected sum-frequency generation spectroscopy is performed at multiple angles of incidence in order to decompose components of the second-order susceptibility tensor when all beams are polarized parallel to the plane of incidence. As an illustration, we study the non-vibrationally resonant gold response. We benchmark our results by comparing with measurements obtained in a polarization scheme that isolates a single element of the susceptibility tensor. Our technique is particularly valuable in the case of metal substrates, where the surface selection rule often prevents spectra from being acquired in multiple beam polarizations.

Monitoring Early Stages of Bacterial Adhesion at Silica Surfaces through Image Analysis.

Bacterial adhesion and biofilm formation on abiotic surfaces are important phenomena with industrial, environmental, and biological relevance. Recent findings using vibrational spectroscopy to study Escherichia coli (E. coli) K12 adhesion on silica indicated that interfacial water signals are linked to changes at the surface in the presence of bacteria. Although such techniques provide a unique glimpse into the surface microenvironment, the origin of the features tracked by the water signals remains to be identified. Here, we have used brightfield microscopy with enhanced image processing to study E. coli K12 adhering to silica. Although most of the clusters of cells on the surface are small, with many individual cells adhered throughout the exponential phase, the overall surface coverage was found to be dominated by clusters greater than 100 µm2 in area. However, it is the adhesion profile of the small clusters that most closely matches the interfacial water signals, suggesting that surface-bound water changes immediately upon adhesion.

Determination of Surface Preference Using Heterospectral Surface-Bulk Correlation Spectroscopy.

We outline a method by which the surface preference of a species in a multicomponent mixture may be obtained using surface-specific visible-infrared sum frequency generation (SFG) spectroscopy combined with bulk infrared absorption and/or Raman data. In general, the problem is complicated by the fact that the SFG signal is a function of both the surface coverage and the structure of the molecules. Two-dimensional correlation analysis can be used to reveal which spectral features are changing synchronously, that is, in phase with each other, and which ones are evolving in a manner that is phase-shifted by 90° (asynchronous correlation) as a function of the bulk composition. We provide a framework for determining the surface preference from the correlations between the vibrational modes in the SFG spectra and between the modes from SFG and bulk infrared and/or Raman spectra. When compared to the equivalent analysis performed using the SFG spectra alone, this method can be used with the data obtained using a single-beam polarization and in congested spectral regions where fitting to isolate the behavior of individual vibrational modes is not robust.

Silica Surface Charge Enhancement at Elevated Temperatures Revealed by Interfacial Water Signals.

The structure of water adjacent to silica is sensitive to the degree of deprotonation of surface silanol groups. As a result, close inspection of signals originating from these water molecules can be used to reveal the surface charge density. We have used nonlinear vibrational spectroscopy of the water O-H stretching band over a temperature range of 10-75 °C to account for the increase in surface potential from deprotonation. We demonstrate that the behavior at the silica surface is a balance between increasing surface charge and a decreasing contribution of water molecules aligned by the surface charge. Together with a model that accounts for two different types of silanol sites, we use our data to report the changes in enthalpy and entropy for deprotonation at each site. This is the first experimental determination of these thermodynamic parameters for hydrated silanol groups at the silica surface, critical to a wide range of geochemical and technological applications.

Adsorption of heptane-toluene binary mixtures on a hydrophobic polymer surface.

Polymer coatings offer a means to modulate the adsorption of molecules onto solid surfaces by offering a surface functionality, charge, roughness, and hydrophobicity that is different from the underlying substrate. One application is to provide anti-fouling functions for metal surfaces. Understanding solvent-surface interactions is an essential component to gaining mechanistic insight into the adsorption process. In this work, we study the adsorption of toluene-heptane binary mixtures onto a perflurorinated polymer surface. We use a combination of IR absorption and Raman scattering spectroscopy to study the mixture in the bulk phase, and surface-specific visible-infrared sum-frequency generation to probe the surface layers. Through the use of homo- and heterospectral two-dimensional correlation spectroscopy, we conclude that the adsorption of the two solvents is reversible and that the surface structure is generally independent of the surface composition, with a small change in toluene orientation as the toluene content increases. We also find that the hydrophobic fluropolymer has very little preference for either solvent, similar to previous studies on hydrophilic surfaces.