Electrochemilumescent sensors : a move in the light direction for new drug detection

[Abstract unavailable

Mixed Ca/Sr salt forms of salicylic acid, tuning structure and aqueous solubility

Ten isostructural single-crystal diffraction studies of mixed cation Ca/Sr salt forms of the salicylate anion are presented, [Ca(1 − x)Srx(C7H5O3)2(OH2)2], where x = 0, 0.041, 0.083, 0.165, 0.306, 0.529, 0.632, 0.789, 0.835 and 1. The structure of an isostructural Sr/Ba species [Sr0.729Ba0.271(C7H5O3)2(OH2)2], is also described. The Ca/Sr structures form a series where, with increasing Sr content, the unit cell expands in both the crystallographic a and c directions (by 1.80 and 3.18% respectively), but contracts slightly in the b direction (−0.31%). The largest percentage structural expansion lies parallel to the direction of propagation of the one-dimensional coordination polymer that is the primary structural feature. This structural expansion is thus associated with increased M—O distances. Aqueous solubility measurements show that solubility generally increases with increasing Sr content·Thus tuning the composition of these mixed counterion salt forms leads to sytematic structural changes and allows solubility to be tuned to values between those for the pure Ca and Sr species

Electrochemiluminescent sensors as a screening strategy for psychoactive substances within biological matrices

With the rapid growth and appearance of novel psychoactive substances (NPS) onto the global drug market, the need for alternative screening methodologies for implementation within clinical environments is substantial. The immunoassay methods currently in use are inadequate for this new drug trend with the potential for misdiagnosis and subsequent administration of incorrect patient treatment increased. This contribution illustrates a strong proof-of-concept for the use of electrochemiluminescence (ECL) as a screening methodology for NPS within biological fluids, using the hallucinogen scopolamine as a model compound. A low cost, easy-to-use and portable sensor has been developed and successfully employed for the detection of scopolamine at clinically relevant concentrations within a variety of biological matrices, including human pooled serum, urine, artificial saliva and sweat, without any prior sample preparation required. Moreover, assessment of the sensor's potential as a point-of-care wearable device was performed with sample collection from the surface of skin, demonstrating its capability for the qualitative identification of scopolamine despite collection of only minimal volumes off the skins surface. The developed sensor described herein exhibits a strong proof-of-concept for the employment of such ECL sensors as point-of-care devices, where the sensors ease of use and removal of time-consuming and complex sample preparation methods will ultimately increase its usability by physicians, widening the avenues where ECL sensors could be employed

Tale of two alkaloids : pH-controlled electrochemiluminescence for differentiation of structurally similar compounds

Electrochemiluminescence (ECL) has increased in popularity as a result of its inherent advantages, including but not limited to portability, simplicity of use, and low reagent consumption. However, its significant advantages are often over shadowed as a result of its limited specificity. ECL emissions are intrinsically broad and lack the definition of other available analytical techniques. Furthermore, species with similar functional groups have almost identical electrochemical behavior and thus typically emit within approximately the same potential region. Within this contribution we have demonstrate the use of pH controlled ECL to prove the presence of two individual species within a mixed sample. Analysis at a single pH would not provide this information. We have illustrated the potential of this methodology to quantify scopolamine alongside sister tropane alkaloid atropine, a known ECL interferent. Previously the two alkaloids could not be distinguished from one another using a single technique which did not involve a separation strategy. pH controlled ECL is a simple approach to improve the specificity of a basic [Ru(bpy)3]2+ film based sensor. By exploiting molecular characteristics, such as pKa, we have been able to fine-tune our methodology to facilitate identification of analytes previously exhibiting indistinguishable ECL emission. Thus, by improving specificity, while maintaining operational simplicity and inexpensive design, we have been able to highlight the potential power of ECL for identification of structurally similar compounds. Further improvements of specificity, such as demonstrated within this contribution, will only further future applications of ECL sensors across a range of different fields

Greater Than the Sum: Systems Thinking in Tobacco control

Tobacco control and public health have evolved into a complex set of interconnected and largely self-organizing systems. Their components include international, national, and local governmental agencies; individual advocacy groups; policy makers; health care professionals; nonprofit foundations; and the general population itself. The issues require the exploration of approaches and methodologies that speak to the evolving, dynamic nature of this systems environment. This monograph focuses on the first two years of the Initiative on the Study and Implementation of Systems (ISIS), which was funded by the National Cancer Institute to examine the potential for systems thinking in tobacco control and public health. ISIS explored the general idea of a systems thinking rubric encompassing a great variety of systems-oriented methodologies and approaches. Four approaches have particular promise for their applicability to tobacco control and public health and thus were chosen as areas for initial investigation: (1) organizing and managing as a system, (2) system dynamics and how to model those dynamics, (3) system networks and their analysis, and (4) systems knowledge and its management and translation. As a transdisciplinary effort that linked both tobacco control stakeholders and systems experts, ISIS combined a number of exploratory projects and case studies within these four approaches with a detailed examination of the potential for systems thinking in tobacco control. Its end product was a set of expert consensus guidelines for the future implementation of systems thinking and systems perspectives for tobacco control and public health.https://cancercontrol.cancer.gov/tcrb/monographs/18/index.htm

New liver cell mutants defective in the endocytic pathway

AbstractTo isolate mutant liver cells defective in the endocytic pathway, a selection strategy using toxic ligands for two distinct membrane receptors was utilized. Rare survivors termed trafficking mutants (Trf2–Trf7) were stable and more resistant than the parental HuH-7 cells to both toxin conjugates. They differed from the previously isolated Trf1 HuH-7 mutant as they expressed casein kinase 2 α″ (CK2α″) which is missing from Trf1 cells and which corrects the Trf1 trafficking phenotype. Binding of 125I-asialoorosomucoid (ASOR) and cell surface expression of asialoglycoprotein receptor (ASGPR) were reduced approximately 20%–60% in Trf2–Trf7 cells compared to parental HuH-7, without a reduction in total cellular ASGPR. Based on 125I-transferrin binding, cell surface transferrin receptor activity was reduced between 13% and 88% in the various mutant cell lines. Distinctive phenotypic traits were identified in the differential resistance of Trf2–Trf7 to a panel of lectins and toxins and to UV light-induced cell death. By following the endocytic uptake and trafficking of Alexa488-ASOR, significant differences in endosomal fusion between parental HuH-7 and the Trf mutants became apparent. Unlike parental HuH-7 cells in which the fusion of endosomes into larger vesicles was evident as early as 20 min, ASOR endocytosed into the Trf mutants remained within small vesicles for up to 60 min. Identifying the biochemical and genetic mechanisms underlying these phenotypes should uncover novel and unpredicted protein–protein or protein–lipid interactions that orchestrate specific steps in membrane protein trafficking

In situ monitoring of powder blending by non-invasive Raman spectrometry with wide area illumination

A 785 nm diode laser and probe with a 6 mm spot size were used to obtain spectra of stationary powders and powders mixing at 50 rpm in a high shear convective blender. Two methods of assessing the effect of particle characteristics on the Raman sampling depth for microcrystalline cellulose (Avicel), aspirin or sodium nitrate were compared: (i) the information depth, based on the diminishing Raman signal of TiO2 in a reference plate as the depth of powder prior to the plate was increased, and (ii) the depth at which a sample became infinitely thick, based on the depth of powder at which the Raman signal of the compound became constant The particle size, shape, density and/or light absorption capability of the compounds were shown to affect the "information" and "infinitely thick" depths of individual compounds. However, when different sized fractions of aspirin were added to Avicel as the main component, the depth values of aspirin were the same and matched that of the Avicel: 1.7 mm for the "information" depth and 3.5 mm for the "infinitely thick" depth. This latter value was considered to be the minimum Raman sampling depth when monitoring the addition of aspirin to Avicel in the blender. Mixing profiles for aspirin were obtained non-invasively through the glass wall of the vessel and could be used to assess how the aspirin blended into the main component, identify the end point of the mixing process (which varied with the particle size of the aspirin), and determine the concentration of aspirin in real time. The Raman procedure was compared to two other non-invasive monitoring techniques, near infrared (NIR) spectrometry and broadband acoustic emission spectrometry. The features of the mixing profiles generated by the three techniques were similar for addition of aspirin to Avicel. Although Raman was less sensitive than NIR spectrometry, Raman allowed compound specific mixing profiles to be generated by studying the mixing behaviour of an aspirin-aspartame-Avicel mixture

Does the salt really matter? Impact of the counterion upon ECL signal

The incorporation of counterions into a variety of substances to control a number of their physiochemical properties is vital within a range of fields. Electrochemiluminescence (ECL) based sensors have grown in popularity in recent years with their employment observed across analytical and bioanalytical applications. ECL is typically concerned with the core electroactive functionality of the species of interest, with structural similarities commonly employed to determine the likelihood of a species ECL capability. However, to date no consideration has been given to the impact of different counterions toward an analytes ECL mechanism. Here we report for the first time how a simple alternation to a co-reactants counterion can significantly impact upon its recorded ECL response. Utilizing the tropane alkaloid scopolamine and its hydrobromide and hydrochloride salt forms, we have seen through interrogation with the traditional ruthenium luminophore, that replacement of the bromide anion for the chloride anion can reduce the electroactivity of the species. Direct comparison between the hydrobromide and hydrochloride salt forms relived differences in respect of their emission potentials and intensities. The impact of the salt form upon the ECL response has here been investigated, in respect to predicted concentrations. Results demonstrated how vastly different concentrations were obtained dependent upon the salt form present within the sample and that which was used to produce the calibration curve. The impact of this discovery will be of interest to the electrochemiluminescent and electroanalytical communities, and in particular forensic practitioners where electrochemical and ECL based sensors are of increasing interest. Ultimately the application of an ECL sensor within an analytical environment relies upon its accuracy and hence a thorough understanding of the phenomenon observed will only stand to widen the acceptance of ECL within the wider analytical community and increase its potential future applications

A practical guide to pre-trial simulations for Bayesian adaptive trials using SAS and BUGS

It is often unclear what specific adaptive trial design features lead to an efficient design which is also feasible to implement. Before deciding on a particular design, it is generally advisable to carry out a simulation study to characterise the properties of candidate designs under a range of plausible assumptions. The implementation of such pre-trial simulation studies presents many challenges and requires considerable statistical programming effort and time. Despite the scale and complexity, there is little existing literature to guide the implementation of such projects using commonly available software. This Teacher's Corner article provides a practical step-by-step guide to implementing such simulation studies including how to specify and fit a Bayesian model in WinBUGS or OpenBUGS using SAS, and how results from the Bayesian analysis may be pulled back into SAS and used for adaptation of allocation probabilities before simulating subsequent stages of the trial. The interface between the two software platforms is described in detail along with useful tips and tricks. A key strength of our approach is that the entire exercise can be defined and controlled from within a single SAS program