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.

Trace Detection of Adulterants in Illicit Opioid Samples Using Surface-Enhanced Raman Scattering and Random Forest Classification.

The detection of trace adulterants in opioid samples is an important aspect of drug checking, a harm reduction measure that is required as a result of the variability and unpredictability of the illicit drug supply. While many analytical methods are suitable for such analysis, community-based approaches require techniques that are amenable to point-of-care applications with minimal sample preparation and automated analysis. We demonstrate that surface-enhanced Raman spectroscopy (SERS), combined with a random forest classifier, is able to detect the presence of two common sedatives, bromazolam (0.32-36% w/w) and xylazine (0.15-15% w/w), found in street opioid samples collected as a part of a community drug checking service. The Raman predictions, benchmarked against mass spectrometry results, exhibited high specificity (88% for bromazolam, 96% for xylazine) and sensitivity (88% for bromazolam, 92% for xylazine) for the compounds of interest. We additionally provide evidence that this exceeds the performance of a more conventional approach using infrared spectral data acquired on the same samples. This demonstrates the feasibility of SERS for point-of-care analysis of challenging multicomponent samples containing trace adulterants.

Beyond a spec: assessing heterogeneity in the unregulated opioid supply.

BACKGROUND: Drug checking services aim to provide compositional information for the illicit drug supply and are being employed in public health responses to extreme rates of overdose associated with fentanyl within street opioids. The technologies used within these services range from basic qualitative tests, such as immunoassay test strips, to comprehensive quantitative analyses, such as mass spectrometry. In general, there is concern that heterogeneity of a drug mixture adds significant uncertainty when using drug checking results based on a small subsamples. The presence of hot spots of active drug components in this context is often termed the 'chocolate chip cookie effect'. Establishing the limitations of the service are essential for interpretation of the results. METHODS: This study assesses the consequence of drug heterogeneity and sampling of consumer level opioid purchased in Victoria, British Columbia ( n = 21 , 50-100 mg each) on quantitative fentanyl results determined from testing with paper spray mass spectrometry. RESULTS: Using descriptive statistics, such as relative standard deviation and interquartile range, the results demonstrate varied distributions of fentanyl concentrations within a single drug batch. However, the presence of hot spots, defined as outliers, were relatively rare. CONCLUSIONS: This study found that the variability in fentanyl concentration from drug heterogeneity and sampling is greater than that attributed to the analytical technique. On a practical level, this provides data to help guide communication of limitations of drug checking services, supporting the aim of trust and transparency between services and people who use drugs. However, if drug checking services continue to be restricted from fully engaging with the reality of manufacturing, buying, selling, mixing and dosing practices, the accuracy, usefulness, and impact will always be limited.

Point-of-care community drug checking technologies: an insider look at the scientific principles and practical considerations.

Drug checking is increasingly being explored outside of festivals and events to be an ongoing service within communities, frequently integrated within responses to illicit drug overdose. The choice of instrumentation is a common question, and the demands on these chemical analytical instruments can be challenging as illicit substances may be more complex and include highly potent ingredients at trace levels. The answer remains nuanced as the instruments themselves are not directly comparable nor are the local demands on the service, meaning implementation factors heavily influence the assessment and effectiveness of instruments. In this perspective, we provide a technical but accessible introduction to the background of a few common drug checking methods aimed at current and potential drug checking service providers. We discuss the following tools that have been used as part of the Vancouver Island Drug Checking Project in Victoria, Canada: immunoassay test strips, attenuated total reflection IR-absorption spectroscopy, Raman spectroscopy from powder samples, surface-enhanced Raman scattering in a solution of colloidal gold nanoparticles, and gas chromatography-mass spectrometry. Using four different drug mixtures received and tested at the service, we illustrate the strengths, limitations, and capabilities of such instruments, and expose the scientific theory to give further insight into their analytical results. Each case study provides a walk-through-style analysis for a practical comparison between data from several different instruments acquired on the same sample. Ideally, a single instrument would be able to achieve all of the objectives of drug checking. However, there is no clear instrument that ticks every box; low cost, portable, rapid, easy-to-use and provides highly sensitive identification and accurate quantification. Multi-instrument approaches to drug checking may be required to effectively respond to increasingly complex and highly potent substances demanding trace level detection and the potential for quantification.

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.

Everywhere and for everyone: proportionate universalism as a framework for equitable access to community drug checking.

BACKGROUND: Illicit drug overdoses have reached unprecedented levels, exacerbated by the COVID-19 pandemic. Responses are needed that address the increasingly potent and unpredictable drug supply with better reach to a wide population at risk for overdose. Drug checking is a potential response offered mainly within existing harm reduction services, but strategies are needed to increase reach and improve equitable delivery of drug checking services. METHODS: The purpose of this qualitative study was to explore how to extend the reach of drug checking services to a wide population at risk of overdose. We conducted 26 in-depth interviews with potential service users to identify barriers to service use and strategies to increase equitable delivery of drug checking services. Our analysis was informed by theoretical perspectives on equity, and themes were developed relevant to equitable delivery through attention to quality dimensions of service use: accessibility, appropriateness, effectiveness, safety, and respect. RESULTS: Barriers to equitable service delivery included criminalization and stigma, geographic and access issues, and lack of cultural appropriateness that deter service use for a broad population with diverse needs. Strategies to enhance equitable access include 1ocating services widely throughout communities, integrating drug checking within existing health care services, reframing away from risk messaging, engaging peers from a broad range of backgrounds, and using discrete methods of delivery to help create safer spaces and better reach diverse populations at risk for overdose. CONCLUSIONS: We propose proportionate universalism in drug checking as a guiding framework for the implementation of community drug checking as an equity-oriented harm reduction intervention and as a population health response. Both a universal equity-oriented approach and multiple tailored approaches are required to facilitate drug checking services that maximize reach and appropriateness to respond to diverse needs.

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.

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.

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.

The potential impacts of community drug checking within the overdose crisis: qualitative study exploring the perspective of prospective service users.

BACKGROUND: As drug checking becomes more integrated within public health responses to the overdose crisis, and potentially more institutionalized, there is value in critically questioning the impacts of drug checking as a harm reduction response. METHODS: As part of a pilot project to implement community drug checking in Victoria, BC, Canada, in-depth interviews (N = 27) were held with people who use or have used substances, family or friends of people who use substances, and/or people who make or distribute substances. Critical harm reduction and social justice perspectives and a socioecological model guided our analysis to understand the potential role of drug checking within the overdose crisis, from the perspective of prospective service users. RESULTS: Participants provided insight into who might benefit from community drug checking and potential benefits. They indicated drug checking addresses a "shared need" that could benefit people who use substances, people who care for people who use substances, and people who sell substances. Using a socioecological model, we identified four overarching themes corresponding to benefits at each level: "drug checking to improve health and wellbeing of people who use substances", "drug checking to increase quality control in an unregulated market", "drug checking to create healthier environments", and "drug checking to mediate policies around substance use". CONCLUSIONS: Drug checking requires a universal approach to meet the needs of diverse populations who use substances, and must not be focused on abstinence based outcomes. As a harm reduction response, community drug checking has potential impacts beyond the individual level. These include increasing power and accountability within the illicit drug market, improving the health of communities, supporting safer supply initiatives and regulation of substances, and mitigating harms of criminalization. Evaluation of drug checking should consider potential impacts that extend beyond individual behaviour change and recognize lived realities and structural conditions.

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.

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.

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.

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.

What is needed for implementing drug checking services in the context of the overdose crisis? A qualitative study to explore perspectives of potential service users.

BACKGROUND: The current illicit drug overdose crisis within North America and other countries requires expanded and new responses to address unpredictable and potentially lethal substances, including fentanyl analogues, in the unregulated drug market. Community-wide drug checking is being increasingly explored as one such public health response. We explored how drug checking could be implemented as a potential harm reduction response to the overdose crisis, from the perspective of potential service users. METHODS: The research was guided by the Consolidated Framework for Implementation Research (CFIR). We conducted a qualitative, pre-implementation study to inform development and implementation of drug checking services that are acceptable to people who use substances and meet their needs. University and community researchers conducted 27 in-depth interviews with potential service users at prospective drug checking sites. We inductively developed emerging themes to inform the implementation of drug checking services within the five domains of the CFIR, and identified the most relevant constructs. RESULTS: Implementing community drug checking faces significant challenges within the current context of criminalization and stigmatization of substance use and people who use/sell drugs, and trauma experienced by potential service users. Participants identified significant risks in accessing drug checking, and that confidential and anonymous services are critical to address these. Engaging people with lived experience in the service can help establish trust. The relative advantage of drug checking needs to outweigh risks through provision of accurate results conveyed in a respectful, non-judgemental way. Drug checking should provide knowledge relevant to using and/or selling drugs and informing one's own harm reduction. CONCLUSIONS: For service users, the extent to which the implementation of drug checking can respond to and mitigate the risks of being criminalized and stigmatized is critical to the acceptability and success of community drug checking. The culture and compatibility of the service, setting and staff with harm reduction principles and practices is essential.

Surface Water as a Mediator and Reporter of Adhesion at Aqueous Interfaces.

Understanding the adsorption of molecules onto surfaces is integral to a wide variety of fields with scientific, engineering, and industrial applications. The surface-adsorbed structure is governed by the nature of the molecule, surface characteristics, and solution environment. There are therefore three critical interactions that govern adhesion: solvent-analyte, substrate-analyte, and substrate-solvent. The last two interactions require a surface-specific probe restricted to a few nanometers or less. This is particularly true of efforts to probe polymer surface structure without being overwhelmed by bulk polymer signal or interfacial water structure in the presence of bulk water. Second-order nonlinear optical techniques are ideal probes of such interactions, as their reporting depth is determined by the polar arrangement of molecules (a break in the macroscopic inversion symmetry) rather than the penetration of the optical fields. This Account begins with an introduction of surface water structure from the perspective of a nonlinear probe. Details about the unique view of the water orientation distribution are discussed and contrasted with information obtained from conventional vibrational techniques. The salient features of water next to model hydrophobic and hydrophilic surfaces are discussed, in preparation for a discussion of solute interactions that follows. We then present three examples using a combination of linear and nonlinear vibrational spectroscopy and molecular dynamics simulations to illustrate how water is both a mediator and a marker of adhesion. The first is a study of amphipathic peptide adhesion onto hydrophobic and hydrophilic surfaces, characterizing the adsorbed structure in relation to the water surrounding the molecule and trapped near the surface. Water is found to be especially important in mediating adhesion to hydrophilic surfaces, where it aids in solvating the peptide as well as facilitating interactions with the surface. In the second example, we look at adhesion of a multicomponent polymer adhesive using surface-bulk heterospectral correlation analysis, in which surface vibrational spectroscopy is combined with bulk infrared absorption to determine interfacial structure development during the evaporation of water. When acrylic acid is added to the polymer, there is a change in orientation of the polymer before an increase in population. This is opposite to what is observed when no additive is present. In our third example, we show how interfacial water provides a unique window into the surface microenvironment during bacterial adhesion, highlighting the role of solution conditions at the surface in cell attachment and biofilm growth. Changes in the nonlinear vibrational response of interfacial water reflect changes occurring in the pH and ionic strength only at the surface, due to the presence of polymeric adhesives secreted by the bacteria. These studies underline the importance of surface water in governing the structure of adhered molecules and in mediating changes in the interfacial environment as a result of adhesion and provide insight into a nanoscale region that is otherwise difficult to query. They also illustrate the importance of combining surface-sensitive and bulk spectroscopic probes with computer modeling to gain a better understanding of the interplay between water and adsorbate structure.

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.

Broadband models and their consequences on line shape analysis in vibrational sum-frequency spectroscopy.

Vibrational sum-frequency generation (SFG) spectroscopy can provide valuable qualitative and quantitative information about molecular species at surface and buried interfaces. For example, the resonance frequency of a particular chemical function group is revealing of the surface environment, especially when compared to what is observed in bulk IR absorption or Raman scattering spectra. Furthermore, the amplitude of the mode can be related to the molecular orientation, providing a detailed quantitative account of the surface structure. Each of these attributes, however, requires fitting the spectra to some vibrationally resonant line shape. This is particularly challenging when the modes of interest co-exist with broad resonance features, such as water O-H stretching. In this perspective, we examine the merits and consequences of different approaches to fitting homodyne SFG data. We illustrate that, while any model can provide a useful description of the data, no model can accurately and consistently provide even the relative phase deeply encoded in homodyne data without the use of additional information.

Ions, metabolites, and cells: Water as a reporter of surface conditions during bacterial growth.

Surface-specific nonlinear vibrational spectroscopy, combined with bulk solution measurements and imaging, is used to study the surface conditions during the growth of E. coli. As a result of the silica high surface charge density, the water structure at the silica-aqueous interface is known to be especially sensitive to pH and ionic strength, and surface concentration profiles develop that can be appreciably different from the bulk solution conditions. We illustrate that, in the presence of growing cells, a unique surface micro-environment is established as a result of metabolites accumulating on the silica surface. Even in the subsequent absence of the cells, this surface layer works to reduce the interfacial ionic strength as revealed by the enhanced signal from surface water molecules. In the presence of growing cells, an additional boost in surface water signal is attributed to a local pH that is higher than that of the bulk solution.