New generation of electrochemical immunoassay based on polymeric nanoparticles for early detection of breast cancer

Screening and early diagnosis are the key factors for the reduction of mortality rate and treatment cost of cancer. Therefore, sensitive and selective methods that can reveal the low abundance of cancer biomarkers in a biological sample are always desired. Here, we report the development of a novel electrochemical biosensor for early detection of breast cancer by using bioconjugated self-assembled pH-responsive polymeric micelles. The micelles were loaded with ferrocene molecules as "tracers" to specifically target cell surface-associated epithelial mucin (MUC1), a biomarker for breast and other solid carcinoma. The synthesis of target-specific, ferrocene-loaded polymeric micelles was confirmed, and the resulting sensor was capable of detecting the presence of MUC1 in a sample containing about 10 cells/mL. Such a high sensitivity was achieved by maximizing the loading capacity of ferrocene inside the polymeric micelles. Every single event of binding between the antibody and antigen was represented by the signal of hundreds of thousands of ferrocene molecules that were released from the polymeric micelles. This resulted in a significant increase in the intensity of the ferrocene signal detected by cyclic voltammetry

Spirobifluorene-based polymers of intrinsic microporosity for the adsorption of methylene blue from wastewater: effect of surfactants

Owing to their high surface area and superior adsorption properties, spirobifluorene polymers of intrinsic microporosity (PIMs), namely PIM-SBF-Me (methyl) and PIM-SBF-tBu (tert-butyl), were used for the first time, to our knowledge, for the removal of methylene blue (MB) dye from wastewater. Spirobifluorene PIMs are known to have large surface area (can be up to 1100 m2 g−1) and have been previously used mainly for gas storage applications. Dispersion of the polymers in aqueous solution was challenging owing to their extreme hydrophobic nature leading to poor adsorption efficiency of MB. For this reason, cationic (cetyl-pyridinium chloride), anionic (sodium dodecyl sulfate; SDS) and non-ionic (Brij-35) surfactants were used and tested with the aim of enhancing the dispersion of the hydrophobic polymers in water and hence improving the adsorption efficiencies of the polymers. The effect of surfactant type and concentration were investigated. All surfactants offered a homogeneous dispersion of the polymers in the aqueous dye solution; however, the highest adsorption efficiency was obtained using an anionic surfactant (SDS) and this seems owing to the predominance of electrostatic interaction between its molecules and the positively charges dye molecules. Furthermore, the effect of polymer dosage and initial dye concentration on MB adsorption were also considered. The kinetic data for both polymers were well described by a pseudo-second-order model, while the Langmuir model better simulated the adsorption process of MB dye on PIM-SBF-Me and the Freundlich model was more suitable for PIM-SBF-tBu. Moreover, the maximum adsorption capacities recorded were 84.0 and 101.0 mg g−1 for PIM-SBF-Me and PIM-SBF-tBu, respectively. Reusability of both polymers was tested by performing three adsorption cycles and the results substantiate that both polymers can be effectively re-used with insignificant loss of their adsorption efficiency (®). These preliminary results suggested that incorporation of a surfactant to enhance the dispersion of hydrophobic polymers and adsorption of organic contaminants from wastewater is a simple and cost-effective approach that can be adapted for many other environmental applications

Origami Chips: Development and validation of a paper-based Lab-on-a-Chip device for the rapid and cost-effective detection of 4-methylmethcathinone (mephedrone) and its metabolite, 4-methylephedrine in urine

4-methylmethcathinone (mephedrone) has emerged in drug seizures as a new psychoactive substance (NPS) causing a public health risk of global concern. Currently, there are no commercial microfluidic devices for the selective detection of mephedrone and so this study presents a simple, low cost and portable paper-based Lab-on-a-Chip (LOC) device with colorimetric detection to fill this gap. Limits of detection for mephedrone in spiked urine and dissolved powder (aqueous) samples are clinically relevant at 4.34 ng mL-1 and 2.51 ng mL-1 respectively. No cross-reactivity for commonly encountered cutting agents, interferents and adulterants were detected. Mephedrone and its main metabolite were detectable in aqueous samples within 3 minutes. Stability and reproducibility measurements showed no significant difference in signal intensity over eight weeks and no significant difference within or between devices. The proposed device has the potential to provide cost-effective, rapid, on-site testing within forensic or clinical settings and therefore has wide global applicability

On-chip polyelectrolyte coating onto magnetic droplets-towards continuous flow assembly of drug delivery capsules

Polyelectrolyte (PE) microcapsules for drug delivery are typically fabricated via layer-by-layer (LbL) deposition of PE layers of alternating charge on sacrificial template microparticles, which usually requires multiple incubation and washing steps that render the process repetitive and time-consuming. Here, ferrofluid droplets were explored for this purpose as an elegant alternative of templates that can be easily manipulated via an external magnetic field, and require only a simple microfluidic chip design and setup. Glass microfluidic devices featuring T-junctions or flow focusing junctions for the generation of oil-based ferrofluid droplets in an aqueous continuous phase were investigated. Droplet size was controlled by the microfluidic channel dimensions as well as the flow rates of the ferrofluid and aqueous phases. The generated droplets were stabilised by a surface active polymer, polyvinylpyrrolidone (PVP), and then guided into a chamber featuring alternating, co-laminar PE solutions and wash streams, and deflected across them by means of an external permanent magnet. The extent of droplet deflection was tailored by the flow rates, the concentration of magnetic nanoparticles in the droplets, and the magnetic field strength. PVP-coated ferrofluid droplets were deflected through solutions of polyelectrolyte and washing streams using several iterations of multilaminar flow designs. This culminated in an innovative "Snakes-and-Ladders" inspired microfluidic chip design that overcame various issues of the previous iterations for the deposition of layers of anionic poly(sodium-4-styrene sulfonate) (PSS) and cationic poly(fluorescein isothiocyanate allylamine hydrochloride) (PAH-FITC) onto the droplets. The presented method demonstrates a simple and rapid process for PE layer deposition in <30 seconds, and opens the way towards rapid layer-by-layer assembly of PE microcapsules for drug delivery applications.The authors thank the Royal Embassy of Saudi Arabia Cultural Bureau in London and Albaha University in Saudi Arabia for funding. J.G.-P., E.B. and I.O. acknowledge financial support from the Spanish Ministry of Economy and Competitiveness (project CTQ2015-66078-R (MINECO/FEDER) and FPI postgraduate research grant (BES-2013-064415). The authors thank Dr Stephen Clark for fabrication of the microfluidic devices

Novel and versatile solid-state chemiluminescence sensor based on TiO2-Ru(bpy)32+ nanoparticles for pharmaceutical drugs detection

This work describes a novel and versatile solid-state chemiluminescence sensor for analyte detection using TiO2-Ru(bpy)32+-Ce(IV). Herein, we report the synthesis, characterization, optimization and application of a new type of hybrid nanoparticles (NPs). Mesoporous TiO2-Ru(bpy)32+ NPs were prepared using a modified sol-gel method by incorporating Ru(bpy)32+ into the initial reaction mixture at various concentrations. The resultant bright orange precipitate was characterized via transmission electron microscopy, N2 sorpometry, inductively coupled plasma-optical emission spectrometer (ICP-OES), Raman and UV-Vis spectroscopy techniques. The concentration of Ru(bpy)32+ complex in the NPs was quantified using ICP-OES, and its chemiluminescence (CL) response was measured and compared with the same concentration in the liquid phase using oxalate as model analyte. The results showed that this type of hybrid material exhibited a higher CL signal compared with the liquid phase due to the enlarged surface area of the hybrid NPs (~149.6 m2/g). The amount of TiO2-Ru(bpy)32+ NPs and the effect of the analyte flow rate were also investigated to optimize the CL signal. The optimized system was further used to detect oxalate and two pharmaceutical drugs, namely, imipramine and promazine. The linear range for both drugs was 1–100 pm with limits of detection (LOD) of 0.1 and 0.5 pm, respectively. This approach is considered to be simple, low cost and facile and can be applied to a wide range of analytes

Magnetic carbon nanoparticles derived from candle soot for SALDI MS analyses of drugs and heavy metals in latent fingermarks

For decades, the analysis of fingerprints (FP) has been used as the primary biometric mean of human identification. In parallel, the chemical analysis of latent fingermark (LFM) with particular reference to “touch chemistry”, offers additional intelligence to forensic examination; as such, continuous improvements in the versatility and sensitivity of detection of the molecular make up of FM is of obvious importance. In this light, we propose a facile approach to synthesize magnetic carbon nanoparticles (MCNPs) from candle soot for extraction and detection of endogenous and exogenous FM components. Initially, endogenous components of FM including fatty acids (FAs), squalene and triacylgycerols (TAGs), were successfully extracted and detected using the developed MCNPs and surface assisted laser desorption/ionization-mass spectrometry (SALDI-MS). Furthermore, the MCNPs enabled the detection of exogenous substances including antihistamine, β-blocker, antibiotic drugs and lead in contaminated FMs, whilst providing characteristic and unique fragmentation patterns for each drugs in the FM. The influence of environmental factors such as temperature on the stability of the exogenous substances in FM was investigated by exposing the contaminated FM to different temperatures over 24 h, the findings revealed the drugs' instability at high temperatures and undergo different degrees of degradation whereas lead was more resilient to thermal stress. The detection of triprolidine, metoprolol and sulfamethoxazole from pharmaceutical tablets in FM was successfully achieved by gently touching the tablet powder. The limit of detection (LOD) values of the drugs in the tablet forms were 50, 200 and 750 ng mL−1 for triprolidine, metoprolol and sulfamethoxazole, respectively and their recovery rates were 91.17% for triprolidine, 94.67% for metoprolol and 120.86% for sulfamethoxazole. Finally, to create a genuine casework scenario, contaminated FM was deposited on glass and metal surfaces then subjected to extraction using MCNPs and magnet without compromising the FM impression. Substrate control experiments revealed that the glass surface exhibiting some background signal, however, they did not interfere with the analysis and satisfactory extraction efficiency of endogenous and exogenous components of the FM on both surfaces was obtained using the MCNPs. Overall, this study proves the capability of MCNPs as new SALDI-MS substrate for both extraction and detection of FM components gathering more information pertaining to the donor's lifestyle

New generation of electrochemical immunoassay based on polymeric nanoparticles for early detection of breast cancer

Fouzi Mouffouk,1 Sihem Aouabdi,2 Entesar Al-Hetlani,1 Hacene Serrai,3 Tareq Alrefae,4 Liaohai Leo Chen5 1Department of Chemistry, Kuwait University, Safat, Kuwait; 2King Abdullah International Medical Research Center (KAIMRC), Jeddah, Kingdom of Saudi Arabia; 3Department of Radiology and Nuclear Medicine, University Hospital of Gent (UZG), Gent, Belgium; 4Department of Physics, Kuwait University, Safat, Kuwait; 5Surgical Precision Research&nbsp;Lab. Department of Surgery, University of Illinois at Chicago, IL,&nbsp;USA Abstract: Screening and early diagnosis are the key factors for the reduction of mortality rate and treatment cost of cancer. Therefore, sensitive and selective methods that can reveal the low abundance of cancer biomarkers in a biological sample are always desired. Here, we report the development of a novel electrochemical biosensor for early detection of breast cancer by using bioconjugated self-assembled pH-responsive polymeric micelles. The micelles were loaded with ferrocene molecules as &ldquo;tracers&rdquo; to specifically target cell surface-associated epithelial mucin (MUC1), a biomarker for breast and other solid carcinoma. The synthesis of target-specific, ferrocene-loaded polymeric micelles was confirmed, and the resulting sensor was capable of detecting the presence of MUC1 in a sample containing about 10 cells/mL. Such a high sensitivity was achieved by maximizing the loading capacity of ferrocene inside the polymeric micelles. Every single event of binding between the antibody and antigen was represented by the signal of hundreds of thousands of ferrocene molecules that were released from the polymeric micelles. This resulted in a significant increase in the intensity of the ferrocene signal detected by cyclic voltammetry. Keywords: electrochemical immunoassay, polymeric nanoparticles, breast cancer biomarkers, biosensors&nbsp