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Current methods for the screening of viral infections in clinical settings, such as reverse transcription polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA), are expensive, time-consuming, require trained personnel and sophisticated instruments. Therefore, novel sensors that can save time and cost are required specially in remote areas and developing countries that may lack the advanced scientific infrastructure for this task. In this work, we present a sensitive, and highly specific biosensing approach for the detection of harmful viruses that have cysteine residues within the structure of their cell surface proteins. We utilized new method for the rapid screening of SARS-CoV-2 virus in biological fluids through its S1 protein by surface enhanced Raman spectroscopy (SERS). The protein is captured from aqueous solutions and biological specimens using a target-specific extractor substrate. The structure of the purified protein is then modified to convert it into a bio-thiol by breaking the disulfide bonds and freeing up the sulfhydryl (SH) groups of the cysteine residues. The formed biothiol chemisorbs favourably onto a highly sensitive plasmonic sensor and probed by a handheld Raman device in few seconds. The new method was used to screen the S1 protein in aqueous medium, spiked human blood plasma, mucus, and saliva samples down to 150 fg/L. The label-free SERS biosensing method has strong potential for the fingerprint identification many viruses (e.g. the human immunodeficiency virus, the human polyomavirus, the human papilloma virus, the adeno associated viruses, the enteroviruses) through the cysteine residues of their capsid proteins. The new method can be applied at points of care (POC) in remote areas and developing countries lacking sophisticated scientific infrastructure.

This study investigated the development and characterization of leucine and magnesium stearate (MgSt) embedded wet milled inhalable ibuprofen (IBF) dry powder inhaler (DPI) formulations. IBF microparticles were prepared by a wet milling homogenization process and were characterized by SEM, FTIR, DSC, XRD and TGA. Using a Twin-Stage Impinger (TSI), the in vitro aerosolization of the formulations with and without carrier lactose was studied at a flow rate of 60± 5 L/min and the IBF was determined using a validated HPLC method. The flow properties were determined by the Carr’s Index (CI), Hausner Ratio (HR) and Angle of Repose (AR) of the milled IBF with 4–6.25% leucine and leucine containing formulations showed higher flow property than those of formulations without leucine. The fine particle fraction (FPF) of IBF from the prepared formulations was significantly (p = 0.000278) higher (37.1 ± 3.8%) compared to the original drug (FPF 3.7 ± 0.9%) owing to the presence of leucine, which enhanced the aerosolization of the milled IBF particles. Using quantitative phase analysis, the XPRD data revealed the crystallinity and accurate weight percentages of the milled IBF in the formulations. FTIR revealed no changes of the structural integrity of the milled IBF in presence of leucine or MgSt. The presence of 2.5% MgSt in the selected formulations produced the highest solubility (252.8 ± 0.6 µg/mL) of IBF compared to that of unmilled IBF (147.4 ± 1.6 µg/mL). The drug dissolution from all formulations containing 4–6.25% leucine showed 12.2–18.6% drug release in 2.5 min; however, 100% IBF dissolution occurred in 2 h whereas around 50% original and dry milled IBF dissolved in 2 h. The results indicated the successful preparation of inhalable IBF microparticles by the wet milling method and the developed DPI formulations with enhanced aerosolization and solubility due to the presence of leucine may be considered as future IBF formulations for inhalation.

This study investigated a systematic approach for producing ibuprofen (IBF) particles with leucine by wet milling. Using a high shear homogenizer, the particles size of the IBF was reduced. Prepared IBF microparticles were freeze-dried and characterized by using Mastersizer, SEM, DSC, XRD, ATR-FTIR, and TGA. The drug saturation solubility and in-vitro dissolution performance were carried out in phosphate buffer solution (PBS, pH 7.4) at 37°C temperature and IBF were determined using a validated HPLC method. The wet-milled method reduced the particle size from 71.3 to 1.7 μm. The minimum particle size of IBF was obtained in 0.05% Tween 80 solution homogenized at 17,000 rpm for 15 min. The saturated solubility (168.7 µg/mL) of the micronized IBF particles with leucine showed higher compared to that of the original IBF (147.4 µg/mL) in PBS solution. The prepared IBF particles containing 2.5-6.25% leucine showed significantly higher IBF release (100%) compared to that of original drug particles (55.9%) in 120 min. The excipient leucine played a major role in enhancing the solubility and dissolution profile of the prepared IBF particles probably by the formation of hydrogen bonding. The developed wet milling was an efficient and robust technique for reducing the particle size of IBF and could be a useful method for manufacturing drug particles with enhanced solubility and dissolution.

The versatile nature of organic conjugated materials renders their flawless integration into a diverse family of optoelectronic devices with light-harvesting, photodetection, or light-emitting capabilities. Classes of materials that offer the possibilities of two or more distinct optoelectronic functions are particularly attractive as they enable smart applications while providing the benefits of the ease of fabrication using low-cost processes. Here, we develop a novel, multi-purpose conjugated small molecule by combining boron-azadipyrromethene (aza-BODIPY) as electron acceptor with triphenylamine (TPA) as end-capping donor units. The implemented donor–acceptor–donor (D–A–D) configuration, in the form of TPA-azaBODIPY-TPA, preserves ideal charge transfer characteristics with appropriate excitation energy levels, with the additional ability to be used as either a charge transporting interlayer or light-sensing semiconducting layer in optoelectronic devices. To demonstrate its versatility, we first show that TPA-azaBODIPY-TPA can act as an excellent hole transport layer in methylammonium lead triiodide (MAPbI3)-based perovskite solar cells with measured power conversion efficiencies exceeding 17%, outperforming control solar cells with PEDOT:PSS by nearly 60%. Furthermore, the optical bandgap of 1.49 eV is shown to provide significant photodetection in the wavelength range of up to 800 nm where TPA-azaBODIPY-TPA functions as donor in near-infrared organic photodetectors (OPDs) composed of fullerene derivatives. Overall, the established versatility of TPA-azaBODIPY-TPA, combined with its robust thermal stability as well as excellent solubility and processability, provides a new guide for developing highly efficient multi-purpose electronic materials for the next-generation of smart optoelectronic devices. Ministry of Education (MOE) National Research Foundation (NRF) Published version Lam Yeng Ming would like to thank the support of the Singapore Ministry of Education Academic Research Fund Tier 2 (Grant No. MOE2019-T2-1-085). Annalisa Bruno and Enkhtur thank the National Research Foundation for the financial support (Grant No. S18-1176-SCRP). Prashant Sonar is thankful to QUT for the financial support from the Australian Research Council (ARC) for the Future Fellowship (Grant No. FT130101337) and QUT core funding (Grant No. QUT/322120-0301/07). Ajay K. Pandey acknowledges support from Australia India Strategic Research Fund (Project AISRF53820).

This review focuses on the biomedical application of mesoporous silica nanoparticles (MSNs), mainly focusing on the therapeutic application of MSNs for cancer treatment and specifically on overcoming the challenges of currently available anthelmintics (e.g., low water solubility) as repurposed drugs for cancer treatment. MSNs, due to their promising features, such as tunable pore size and volume, ability to control the drug release, and ability to convert the crystalline state of drugs to an amorphous state, are appropriate carriers for drug delivery with the improved solubility of hydrophobic drugs. The biomedical applications of MSNs can be further improved by the development of MSN-based multimodal anticancer therapeutics (e.g., photosensitizer-, photothermal-, and chemotherapeutics-modified MSNs) and chemical modifications, such as poly ethyleneglycol (PEG)ylation. In this review, various applications of MSNs (photodynamic and sonodynamic therapies, chemotherapy, radiation therapy, gene therapy, immunotherapy) and, in particular, as the carrier of anthelmintics for cancer therapy have been discussed. Additionally, the issues related to the safety of these nanoparticles have been deeply discussed. According to the findings of this literature review, the applications of MSN nanosystems for cancer therapy are a promising approach to improving the efficacy of the diagnostic and chemotherapeutic agents. Moreover, the MSN systems seem to be an efficient strategy to further help to decrease treatment costs by reducing the drug dose.

Thiabendazole (TBZ) is an anthelmintic drug currently studied for anticancer purposes. However, due to its low solubility, its biomedical application has been limited. Using mesoporous silica nanoparticles (MSNPs), such as Mobil Composition of Matter Number 41 (MCM-41), as a drug carrier, is a promising approach to improve the solubility of low water-soluble drugs. In the present work, we aim to develop TBZ-loaded MCM-41 (TBZ MCM-41) nanoparticles to improve the solubility and the therapeutic efficacy of TBZ against prostate cancer PC-3 cells. TBZ MCM-41 nanoparticles were synthesized with a size of 215.9 ± 0.07 nm, a spherical shape, a hexagonal array of channels, and a drug loading capacity of 19.1%. The biological effects of the nanoformulation on PC-3 cells were then evaluated using a 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT), IncuCyte live-cell imaging system, cell migration, and reactive oxygen species (ROS) assays. The results demonstrated that TBZ was released from MCM-41 nanoparticles in a controlled manner at pH values of 1.2 and 6.8. The cell viability measurements revealed that the TBZ MCM-41 nanoparticles caused a considerable 2.8-fold increase in the cytotoxicity of TBZ (IC50 127.3 and 46 μM for TBZ and TBZ MCM-41 nanoparticles, respectively). The results of the proliferation assay were in agreement with those of the cell viability measurements, where the MCM-41 increased the cytotoxicity of TBZ in a concentration-dependent manner. Also, the TBZ MCM-41 nanoparticles were found to enhance the potency of the drug and inhibit PC-3 cell migration. In addition, the ROS assay confirmed that TBZ MCM-41 nanoparticles were approximately 15% more potent than TBZ to produce ROS. Overall, the results demonstrated that MCM-41 nanoparticles are a promising carrier to improve the therapeutic efficacy of TBZ against PC-3 cells and suggest evaluating the efficacy of the formulation in vivo.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a serious threat to human health. Current methods such as reverse transcription polymerase chain reaction (qRT-PCR) are complex, expensive, and time-consuming. Rapid, and simple screening methods for the detection of SARS-CoV-2 are critically required to fight the current pandemic. In this work we present a proof of concept for, a simple optical sensing method for the screening of SARS-CoV-2 through its spike protein subunit S1. The method utilizes a target-specific extractor chip to bind the protein from the biological specimens. The disulfide bonds of the protein are then reduced into a biothiol with sulfhydryl (SH) groups that react with a blue-colored benzothiazole azo dye-Hg complex (BAN-Hg) and causes the spontaneous change of its blue color to pink which is observable by the naked eye. A linear relationship between the intensity of the pink color and the logarithm of reduced S1 protein concentration was found within the working range 130 ng.mL

The clinical utilization of fenbendazole (FBZ) as a potential anticancer drug has been limited due to its low water solubility, which causes its low bioavailability. The development of a drug nanoformulation that includes the solubilizing agent as a drug carrier can improve solubility and bioavailability. In this study, Mobil Composition of Matter Number 48 (MCM-48) nanoparticles were synthesized and functionalized with succinylated β-lactoglobulin (BLG) to prevent early-burst drug release. The BLG-modified amine-functionalized MCM-48 (MCM-BLG) nanoparticles were loaded with FBZ to produce the drug nanoformulation (FBZ-MCM-BLG) and improved the water solubility and, consequently, its anticancer effects against human prostate cancer PC-3 cells. The prepared FBZ-MCM-BLG was characterized in terms of size, zeta potential, drug loading capacity, morphology, thermal and chemical analyses, drug release, cellular uptake, cell viability, cell proliferation, production of reactive oxygen species (ROS), and cell migration. The results demonstrated that the FBZ-MCM-BLG nanoparticles have a spherical morphology with a size and zeta potential of 369 ± 28 nm and 28 ± 0.4 mV, respectively. The drug loading efficiency of the new nanoformulation was 19%. The release of FBZ was pH-dependent; a maximum cumulative release of about 76 and 62% in 12 h and a burst release of 53 and 38% in the first 0.5 h was observed at pH 1.2 and 6.8, respectively. The prepared FBZ-MCM-BLG formulation demonstrated higher cytotoxicity effects against PC-3 cells by 5.6- and 1.8-fold, respectively, when compared to FBZ and FBZ-MCM nanoparticles. The new formulation also increased the production of ROS by 1.6- and 1.2-fold and inhibited the migration of PC-3 cells when compared to the FBZ and FBZ-MCM nanoparticles, respectively. Overall, FBZ-MCM-BLG nanoparticles improved FBZ delivery to PC-3 cells and have the potential to be evaluated for the treatment of prostate cancer following a comprehensive in vivo study.

In this work, we utilise the disulphide bond structure of insulin and a new benzothiazole Raman probe for the detection of human insulin using surface-enhanced Raman spectroscopy (SERS). The disulphide bond structure of the insulin was reduced to generate free sulfhydryl terminal groups. When reacted with benzothiazole-functionalised gold nanoparticles, the reduced protein desorbs the Raman probe and causes its Raman signal intensity to quench. Using this approach, insulin was quantified in the concentration range of 1 × 10-14 -1 × 10-8 M by SERS quenching. The limit of quantification of insulin by the SERS quenching method was found to be 1 × 10-14 M (0.01 pM or 58 pg/L), which satisfies the requirements for monitoring its blood concentration in patients. Because many proteins and peptides have disulphide bonds in their molecular structures, the new SERS quenching method has a strong potential for the rapid determination of ultralow concentrations of proteins in formulations and biological fluids.

The molecular structure of many proteins contains disulfide bonds between their cysteine residues. In this work we demonstrate the utilization of the disulfide bond structure of proteins for their label-free determination by surface-enhanced Raman spectroscopy (SERS). The new approach for label-free SERS detection of proteins is demonstrated for human insulin. The protein was selectively extracted from spiked plasma samples using target-specific functionalized nanomaterial. Enzyme-linked immune assay (ELISA) was used to detect insulin in the blood plasma and cross-validate the SERS method. The disulfide bonds in the molecular structure of the protein were chemically reduced and used for their chemisorption onto the gold-coated copper oxide substrate in a unified orientation at a very short distance from the hotspots. The oriented chemisorption of the protein caused significant enhancement to the signal intensity of its Raman vibration modes. This is attributed to the strong short-range electromagnetic and chemical enhancement effects that are experienced by the immobilized protein. Using this approach, label-free and reproducible SERS detection of insulin, down to 10 zM (relative standard deviation [RSD] = 5.52%), was achieved. Sixty-five percent of proteins contain disulfide bonds in their molecular structure. Therefore, the new label-free SERS detection method has strong potential for the determination of ultralow concentrations of proteins at pathology labs and in biology research.

Low water solubility and thus low bioavailability limit the clinical application of fenbendazole (FBZ) as a potential anticancer drug. Solubilizing agents, such as Mobil Composition of Matter Number 41 (MCM) as a drug carrier, can improve the water solubility of drugs. In this study, PEGylated MCM (PEG-MCM) nanoparticles (NPs) were synthesized and loaded with FBZ (PEG-MCM-FBZ) to improve its solubility and, as a result, its cytotoxicity effect against human prostate cancer PC-3 cells. The loading efficiency of FBZ onto PEG-MCM NPs was 17.2%. The size and zeta potential of PEG-MCM-FBZ NPs were 366.3 ± 6.9 nm and 24.7 ± 0.4 mV, respectively. They had a spherical shape and released the drug in a controlled manner at pH 1.2 and pH 6.2. PEG-MCM-FBZ were found to inhibit the migration of PC-3 cells, increase the cytotoxicity effects of FBZ against PC-3 cells by 3.8-fold, and were more potent by 1.4-fold, when compared to the non-PEGylated NPs. In addition, PEG-MCM-FBZ promoted the production of reactive oxygen species by 1.3- and 1.2-fold, respectively, when compared to FBZ and MCM-FBZ. Overall, the results demonstrate that PEG-MCM-FBZ NPs enhanced FBZ delivery to PC-3 cells, therefore, they have the potential to treat prostate cancer after a comprehensive in vivo study.

Cardiac troponin I (cTnI) is a sensitive biomarker for cardiovascular disease (CVD). Rapid determination of cTnI concentration in blood can greatly reduce the potential of significant heart damage and heart failure. Herein, we demonstrate a new electrochemical immunosensor for selective affinity binding and rapid detection of cTnI in blood plasma by an electrochemical method. A conductive film of “poly 2,5-bis(2-thienyl)3,4-diamine-terthiophene (PDATT)” was deposited onto an Indium Tin Oxide (ITO) electrode using chronoamperometry. Anti-cardiac troponin I antibody was then attached to the two amine (NH2) groups substituted on the central thiophene of terthiophene repeating unit of the polymer chain via amide bond formation. The gaps on the surface of the antibody coated immunosensor were backfilled with bovine serum albumin (BSA) to prevent nonspecific binding of interfering molecules. Differential pulse voltammetry (DPV) was used to determine cTnI upon the formation of cTnI immunocomplex on the sensing surface, appearing a peak at 0.27 V. The response range was 0.01–100 ng mL−1 with limit of quantification down to 0.01 ng mL−1. The developed immunosensor was used to determine cTnI in spiked blood plasma without interference from cardiac troponin T (cTnT). Therefore, this new sensor can be utilised for the detection of cTnI biomarker in pathological laboratories and points of care in less than 15 min.

In this work, we demonstrate the fabrication of disposable and field deployable nanostructured conductive substrates for dual detection by Surface Enhanced Raman Scattering (SERS) and electrochemistry. Using a one-step potentiostatic process, gold nanostructures were electrodeposited on three substrates: bare indium tin oxide (ITO) electrode, ITO coated with plane gold and carbon fibre (CF) covered with ZnO nanowires (ZnO NWs). Their sensitivities were enhanced by incorporating the plane gold layer and ZnO NWs. The intensity of SERS signals produced on the nanostructured ITO substrates with 0.1 μM quinolinethiol were of the order: nanostructured gold-coated ITO > nanostructured bare ITO. The higher SERS signal on the nanostructured gold-coated ITO was attributed to the coupling between the surface plasmon polariton provided by the gold under layer and the surface plasmon resonance of the Au nanostructures. The ZnO NWs on the carbon fibre provided additional surface area for electrodeposition of gold nanostructures at high density. This led to multiple hotspots formation yielding high SERS signal intensity relative to that on a nanostructured bare carbon fibre. The nanostructured substrates, demonstrated good SERS signal reproducibility with relative standard deviation of 5.19%, 3.28% and 4.53% for Au/ITO, Au/Au-ITO and Au/ZnO-CF respectively. To demonstrate the potential application of these substrates and estimate their sensitivities, they were used to detect melamine by SERS at 1 pM (for Au nanostructures on bare ITO), 1 fM (for Au nanostructured gold-coated ITO), and 0.1 nM (for Au nanostructures on ZnO NWs-coated CF) concentrations with LOD of 0.118 pM, 0.189 fM and 57.4 pM respectively. Taking advantage of the conductive properties of gold nanostructured ITOs, electrochemical detection of 0.1 μM melamine (with an LOD of 0.05 μM) was also demonstrated. Hence, these substrates are potentially useful for SERS and electrochemical-based detection of organic toxicants.

Due to its high analytical sensitivity and field deplorability, surface enhanced Raman spectroscopy (SERS) has emerged as an analytical tool for detecting environmental toxicants in different matrices. Progress has been made towards development of methods for depositing nanostructures onto solid platforms to design SERS substrates. The properties of the solid platforms used for SERS substrates fabrications such as electrical and heat conductivity, malleability and foldability, have significant influence on then design of the nanostructures and are critical for SERS technique. This review takes a look at recent advances in commonly employed conductive solid materials such as indium tin oxide, carbon fiber, silicon wafers, polyaniline fiber and carbon nanotubes as the supporting platforms for fabricating SERS substrates. It also examines their influence on the fabrication method, the morphology of the nanostructures formed as well as the hot spot density on the resultant novel SERS substrates. Real world applications of these substrates for the detection of environmental toxicants over the past decade have been shown. The review indicates that while significant advances have been made on the use of the conductive properties of these support platforms for SERS substrate fabrication, their subsequent application to detect environmental toxicants have not been fully explored.

A sensitive and recyclable plasmonic nickel foam sensor has been developed for surface-enhanced Raman spectroscopy (SERS). A simple electrochemical method was used to deposit flower-shaped gold nanostructures onto nickel foam substrate. The high packing of the gold nanoflowers onto the nickel foam led to a high enhancement factor (EF) of 1.6 &times, 1011. The new SERS sensor was utilized for the direct determination of the broad-spectrum &beta, lactam carbapenem antibiotic meropenem in human blood plasma down to one pM. The sensor was also used in High Performance Liquid Chromatography (HPLC)-SERS assembly to provide fingerprint identification of meropenem in human blood plasma. Moreover, the SERS measurements were reproducible in aqueous solution and human blood plasma (RSD = 5.5%) and (RSD = 2.86%), respectively at 200 &micro, g/mL (n = 3), and successfully recycled using a simple method, and hence, used for the repeated determination of the drug by SERS. Therefore, the new sensor has a strong potential to be applied for the therapeutic drug monitoring of meropenem at points of care and intensive care units.

Recombinant human erythropoietin (rHuEPO) is an important hormone drug that is used to treat several medical conditions. It is also frequently abused by athletes as a performance enhancing agent at sporting events. The time window of the rHuEPO in blood is short. Therefore, the rapid detection of rHuEPO use/abuse at points of care and in sports requires a selective analytical method and a sensitive sensor. Herein, we present a highly selective method for the rapid detection of rHuEPO in human blood plasma by a sensitive optical sensor. rHuEPO is selectively extracted from human blood plasma by a target-specific extractor chip and converted into a biothiol by reducing its disulfide bond structure. The formed biothiol reacts with a water soluble (E)-1-((6-methoxybenzo[d]thiazole-2-yl)diazenyl)naphthalene-2,6-diolHg(ii) (BAN-Hg) optical sensor and causes its rapid decomposition. This leads to a rapid change in the sensor color from blue to pink that can be observed by the naked eye. The optical sensor was used to quantify rHuEPO in the concentration range 1 × 10-8 M to 1 × 10-12 M by UV-Vis spectroscopy. For the screening of blood plasma, an EPO-specific extractor chip was synthesized and used to selectively extract the protein from the biological matrix prior to its conversion into biothiol and quantification by the optical sensor. Since many proteins have a disulfide bond structure, the new method has strong potential for their rapid sensitive and selective detection by the BAN-Hg sensor and UV-Vis spectroscopy.

We present a sensitive label-free surface enhanced Raman spectroscopy (SERS) method for the discrimination between the recombinant and endogenous human Erythropoietin (EPO) isoforms. The proposed methodology comprises a lectin-functionalised extractor chip for the extraction of the recombinant human EPO (rhuEPO) and the endogenous EPO (enEPO) from blood plasma. The disulfide bond molecular structure of the purified isoforms was modified to chemisorb the biomolecules onto a SERS substrate in a unified orientation, thus maximizing the reproducibility and sensitivity of the SERS measurements. The acquired SERS spectra of the EPO isoforms showed diagnostic Raman bands that allowed for the discrimination between rhuEPO and enEPO. The method was also used for the SERS quantification of rhuEPO and enEPO down to 0.1 pM and 0.5 pM, respectively. The SERS determination of the protein isoforms was cross validated against ELISA. The new SERS method has strong potential for the rapid screening of rhuEPO doping in athletes and for the therapeutic drug monitoring of rhuEPO treatment in cancer patients.

In this work, we propose a new sensitive, selective and portable surface enhanced Raman spectroscopy (SERS) methodology for the rapid on site detection of Pb(II) pollution in water. The new method utilises aminobenzo-18-crown-6 (AB18C6) as a selective recognition molecule to form a spontaneous complex with Pb(II) ions. The formed AB18C6-Pb(II) complex was rapidly immobilised onto a nanostructured gold substrate via Au-N bond formation and reproducibly screened by SERS using a handheld Raman device. For the SERS measurements, a substrate was fabricated by electrochemical deposition of gold nanostructures onto a flat gold disc, creating multiple hotspots for ultrasensitive SERS measurements. The limit of quantification (LOQ) for Pb(II) ions by the SERS method was 2.20 pM. The limit of detection (LOD) was 0.69 pM which is five orders of magnitude lower than the maximum Pb(II) level of 72 nM allowed by the US Environmental Protection Agency. The high sensitivity of the SERS substrate is attributed to the coupling between the Surface Plasmon Polariton (SPP) of its gold surface, the localised Surface Plasmon Resonance (SPR) of the gold nanostructures and the Raman radiation from the immobilised AB18C6-Pb(II) complex. The new SERS detection method was successfully applied for the selective and rapid screening of Pb(II) ion contamination in water proving its practical application for environmental analysis.

Graphical abstract Inhalation of Edoxaban DPI formulation for anticoagulation effect., Herein, we demonstrated the development and characterization of a dry powder inhaler (DPI) formulation of edoxaban (EDX); and investigated the in-vitro anticoagulation effect for the management of pulmonary or cerebral coagulopathy associated with COVID-19 infection. The formulations were prepared by mixing the inhalable micronized drug with a large carrier lactose and dispersibility enhancers, leucine, and magnesium stearate. The drug-excipient interaction was studied using X-Ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) methods. The drug and excipients showed no physical inter particulate interaction. The in-vitro drug aerosolization from the developed formulation was determined by a Twin Stage Impinger (TSI) at a flow rate of 60 ± 5 L /min. The amount of drug deposition was quantified by an established HPLC-UV method. The fine particle fraction (FPF) of EDX API from drug alone formulation was 7%, whereas the formulations with excipients increased dramatically to almost 7-folds up to 47%. The developed DPI formulation of EDX showed a promising in-vitro anticoagulation effect at a very low concentration. This novel DPI formulation of EDX could be a potential and effective inhalation therapy for managing pulmonary venous thromboembolism (VTE) associated with COVID-19 infection. Further studies are warranted to investigate the toxicity and clinical application of the inhaled EDX DPI formulation.

Cyanide (CN−) is one of the most hazardous ions to humans and the environment. Therefore, sensitive, and selective sensors for CN− monitoring are highly required. A novel chemosensor based on naphthalene flanked diketopyrrolopyrrole dye (TBC-DPPN) is synthesized for the direct detection of CN− in water samples by naked eye and vibrational spectroscopy (UV–Vis and fluorescence). The electron deficient carbonyl group of the lactam ring of TBC-DPPN undergoes a nucleophilic attack by the CN− thus causing the yellow color of the dye turn to colorless, and fluorescence of the dye at 527 nm to turn-off. The mechanism of CN− sensing by the TBC-DPPN sensor is confirmed by spectral measurements and density functional theory (DFT) calculations. The TBC-DPPN sensor is utilized to determine the CN− by colorimetric and fluorescence methods in water down to 0.5 and 0.05 µm, respectively, which is well below the cut off limit of 1.9 µm that is recommended by the World Health Organization (WHO). Therefore, TBC-DPPN can act as dual channel sensor with high selectivity and sensitivity for the determination of CN− in water.

Highlights - Sofosbuvir metabolite was studied for the first time by Raman spectroscopy. - Cheap and disposable paper substrate was utilized for the determination of PSI-6206 by HPLC-SERS. - The use of disposable substrate eliminated the memory effect problem in the HPLC-SERS. - The SERS LOQ of PSI-6206 was 13 ng L-1 (R2 = 0.959, RSD = 5.23%), 4 orders of magnitude less than HPLC-DAD. - The HPLC-SERS method provided unique structural identification of PSI-6206 similar to HPLC-MS Abstract Sofosbuvir metabolite, 2′-deoxy-2′-fluoro-2′-C-methyluridine (PSI-6206) was studied for the first time by surface enhanced Raman spectroscopy (SERS) using the paper-based SERS substrate. The quantification limit of PSI-6206 by SERS was found to be 13 ng L−1 (R2 value = 0.959, RSD = 5.23%). For the structural and quantitative analysis of PSI-6206 in blood plasma, an interference-free HPLC-SERS method was developed and compared to HPLC-DAD and HPLC–MS methods. The SERS quantification of the drug by the paper substrate was 4 orders of magnitude more sensitive than that by the diode array detector. In addition, the SERS detection provided unique structural identification of the drug in blood plasma, similar to Mass spectroscopy detector. Due to the disposable nature of the SERS substrate, the new method does not suffer from the known “memory effect” which is known to lead to false positive identification in traditional HPLC-SERS methods. Therefore, the presented HPLC-paper SERS platform holds great potential for the sensitive and cost effective determination of drugs and their metabolites in biological fluids.

Infliximab (INF) is a chimeric monoclonal immunoglobulin acting against tumor necrosis factor-alpha (TNF-α). The drug is used for the treatment of chronic autoimmune and inflammatory diseases. A target-specific nanomaterial is presented for the extraction of INF from human plasma along with a label-free surface enhanced Raman spectroscopy (SERS) method for its determination using a handheld device. A gold-coated copper oxide chip was functionalized with TNF-α and used to extract the drug from plasma. INF was recovered from the extractor by lowering the pH value to 2.5. The disulfide bond structure of the drug was then reduced and used for its oriented chemisorption onto a gold-coated copper oxide substrate for SERS measurements using the INF-specific band at 936 cm −1. The working range of the SERS method was between 10 −7 and 10 −14 M of reduced INF. The relative standard deviation (RSD), between three different measurements was 4.2% (intra-day) and 7.1% (inter-day). The quantification and detection limits of the assay (LOQ, LOD) were 0.01 pM and 1.4 fM respectively. The SERS detection was cross-validated against ELISA where 99% agreement was found between the two methods. [Figure not available: see fulltext.]

The detection of anti-TNF-α drugs require rapid, selective and sensitive biosensors that can be easily utilised at the point of care. Herein, we demonstrate a new biosensing approach that employs target-specific nanomaterial and label free surface-enhanced Raman spectroscopy (SERS) for the selective extraction and rapid determination of Adalimumab (ADB) in human blood plasma. The new method utilises the tumour necrosis factor (TNF-α) for the fabrication of a target-specific nanomaterial for extraction of ADB. The method also uses the thiol chemistry of the purified antibody drug for its chemisorption onto a gold-coated copper oxide substrate. A handheld Raman spectrophotometer is used for the determination of ADB by label free SERS. The limits of quantification (LOQ) and detection (LOD) of the purified and reduced drug by SERS were 0.10 fM and 0.03 fM respectively. ELISA was used for the cross validation of the SERS quantification of ADB where a 98.8% agreement was found between the two methods. Many proteins have disulfide bonds in their molecular structure. Therefore, the demonstrated biosensing approach can be extended for the rapid screening of other proteins and antibody drugs by developing target-specific extractor nanomaterial and utilizing the disulfide bond structure of the purified biomolecules for their label free SERS detection.

A new benzothiazole azo dye [(E)-1-((6-methoxybenzo[d]thiazole-2-yl)diazenyl)naphthalene-2,6-diol] (also known as “BAN”), has been synthesised and used as a chemosensor for the rapid and selective detection of mercury(II) ions in water. The pink coloured chemosensor turns blue when reacted with mercury(II) ions due to the formation of a 2 : 1 coordination complex. The complex formation causes a bathochromic shift of the chemosensor's UV absorption peak from 540 to 585 nm and turns on a highly selective fluorescence emission at 425 nm. The change in the optical property of BAN upon complexation with mercury(II) was confirmed by ab initio calculations. The new chemosensor was used to quantify mercury(II) ions in water by fluorescence spectroscopy down to 5 × 10−8 M (10 ppb). The limit of detection (LOD) of Hg2+ was 9.45 nM (1.8 ppb) which satisfies the maximum allowable Hg2+ concentration in drinking water that is set by the WHO. The BAN–Hg(II) complex was used for the determination of cysteine (Cys) in aqueous solution by UV-Vis spectroscopy down to 1 × 10−7 M. The thiol-containing amino acid preferentially coordinates the mercury ions of the BAN–Hg(II) complex. This causes dissociation of the blue-coloured complex and the liberation of the pink-coloured BAN dye. The colour change of the BAN–Hg(II) complex from blue to pink was selective to the Cys biothiol while other non-thiol containing amino acids did not cause a colour change. For the in-field application, filter paper strips were loaded with the BAN–Hg(II) complex and used as a disposable sensor for the detection of cysteine (Cys) by the naked eye. Therefore, the BAN chemosensor offers a sensitive, and rapid tool for the detection of mercury(II) in water. In addition, the BAN–Hg(II) complex can be used as a simple and selective chemosensor of the screening of purified biothiols, such cysetine, homocysteine and glutathione in biology research and pharmaceutical/food industries.

Isolating, purifying, and identifying proteins in complex biological matrices are often difficult, time consuming, and unreliable. Herein we describe a rapid screening technique for proteins in biological matrices that combines selective protein isolation with direct surface enhanced Raman spectroscopy (SERS) detection. Magnetic core gold nanoparticles were synthesized, characterized, and subsequently functionalized with recombinant human erythropoietin (rHuEPO)-specific antibody. The functionalized nanoparticles were used to capture rHuEPO from horse blood plasma within 15 min. The selective binding between the protein and the functionalized nanoparticles was monitored by SERS. The purified protein was then released from the nanoparticles' surface and directly spectroscopically identified on a commercial nanopillar SERS substrate. ELISA independently confirmed the SERS identification and quantified the released rHuEPO. Finally, the direct SERS detection of the extracted protein was successfully demonstrated for in-field screening by a handheld Raman spectrometer within 1 min sample measurement time.The rapid detection of recombinant human erythropoietin (rHuEPO) is important in competitive sports to screen for doping offences. In this article, the authors reported their technique of direct surface enhanced Raman spectroscopy (SERS) detection using magnetic core gold nanoparticles functionalized with recombinant human erythropoietin-specific antibody. The findings should open a new way for future detection of other proteins.

2,4,6-trinitrotoluene (TNT) is one of the most commonly used nitro aromatic explosives in landmine, military and mining industry. This article demonstrates rapid and selective identification of TNT by surface-enhanced Raman spectroscopy (SERS) using 6-aminohexanethiol (AHT) as a new recognition molecule. First, Meisenheimer complex formation between AHT and TNT is confirmed by the development of pink colour and appearance of new band around 500 nm in UV-visible spectrum. Solution Raman spectroscopy study also supported the AHT:TNT complex formation by demonstrating changes in the vibrational stretching of AHT molecule between 2800-3000 cm−1. For surface enhanced Raman spectroscopy analysis, a self-assembled monolayer (SAM) of AHT is formed over the gold nanostructure (AuNS) SERS substrate in order to selectively capture TNT onto the surface. Electrochemical desorption and X-ray photoelectron studies are performed over AHT SAM modified surface to examine the presence of free amine groups with appropriate orientation for complex formation. Further, AHT and butanethiol (BT) mixed monolayer system is explored to improve the AHT:TNT complex formation efficiency. Using a 9:1 AHT:BT mixed monolayer, a very low detection limit (LOD) of 100 fM TNT was realized. The new method delivers high selectivity towards TNT over 2,4 DNT and picric acid. Finally, real sample analysis is demonstrated by the extraction and SERS detection of 302 pM of TNT from spiked.

Meropenem (MPN), a broad spectrum β-lactam antibiotic, has been increasingly used in the treatment of moderate to severe bacterial infections. However, due to its short plasma half-life and chemical instability in solution form, it has been challenging to use in the intravenous formulation. This study aims to develop and characterize MPN dry powder inhaler (DPI) formulation for pulmonary delivery. The inhalable MPN particles (1-5µm) were prepared by micronization. Lactose, L-leucine and magnesium stearate (MgSt) were used in the powder formulation as carriers and dispersibility enhancers. The formulations were characterized by Scanning electron microscopy (SEM), Transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), Raman confocal microscopy, X-Ray powder diffraction analysis (PXRD), and differential scanning calorimetry (DSC) methods. The concentration of MPN was determined by using a validated HPLC method. The Fine Particle Fraction (FPF) of meropenem from powder mixtures was determined by a Twin Stage Impinger (TSI) at a flow rate of 60 L/min. The FPF of the original MPN was 1.91 % which was significantly increased to 37.5 % for the formulations with excipients. No physical interactions between the drug and the excipients observed. This study revealed the potential of a stable meropenem DPI formulation for pulmonary delivery.

Tumor necrosis factor alpha (TNF-α) is a cytokine that plays a critical role in medical conditions such cardiovascular diseases, rheumatoid arthritis, inflammatory bowel disease, Alzheimer’s and cancer. Herein, we present a new method for the determination of TNF-α by surface enhanced Raman spectroscopy (SERS). A new benzothiazole azo dye (BAN) was used as a Raman probe to detect the cytokine after its selective extraction from blood plasma using a target-specific antibody-functionalised extractor chip. The disulfide bond structure of the extracted TNF-α was reduced to generate free sulfhydryl (SH), terminal groups that adsorb preferentially onto a BAN-functionalised SERS substrate and displace the BAN Raman reporter on the substrate surface. This causes the SERS spectrum of BAN to quench proportionally with the cytokine concentration. Using this SERS quenching sensor, TNF-α was quantified down to 1 × 10−14 M (173 pg/L). The quantification of the cytokine by the SERS quenching method was cross-validated against enzyme-linked immunosorbent assay (ELISA) and the percent agreement between the two measurements was found to be 93.39 %. Since many proteins and peptides have disulfide bonds in their molecular structures, the new SERS quenching method can be extended for their ultrasensitive quantification after selective extraction from biological fluids.

We demonstrate a novel method for the selective extraction and electrochemical detection of S100β disease biomarker. The protein is extracted from blood plasma using target-specific gold coated magnetic nanoparticles. This is followed by the rapid reduction of the disulfide bond structure of the purified protein using chronoamperometry and its immobilisation onto a nanostructured gold electrode. The protein concentration is quantified down to 10 pM (120 ng l−1), by electrochemical desorption using differential pulse voltammetry (DPV). The new method was used to extract and determine S100β in spiked blood plasma and the DPV quantification was cross-validated against enzyme-linked immunosorbent assay (ELISA) where the percent agreement between the two measurements was 96.54%. Therefore, this method has strong potential for the sensitive determination of S100β. In addition, 65% of proteins have similar disulfide bond structure. Therefore, the new method can be utilised for the determination of many disease biomarkers after optimizing specific extractor nanomaterial for the target biomarker.

The detection of protein biomarkers for the clinical diagnosis of diseases requires selective and sensitive methodologies and biosensors that can be easily used at pathology laboratories and points of care. An ideal methodology would be able to conduct multimode screening of low and high concentrations of proteins in biological fluids using recyclable platforms. In this work, we demonstrate a novel nanosensing methodology for the dual detection of cystatin C (CST-C), as a protein biomarker model, in blood plasma by surface-enhanced Raman spectroscopy and electrochemistry. The new methodology utilizes the thiol chemistry of biomolecules to develop a target-specific and recyclable extractor chip for the rapid isolation of protein biomarkers from blood plasma. This is followed by the rapid reduction of the disulfide bonds within the isolated protein to influence its oriented immobilization onto a conductive gold coated silicon nanopillar substrate via stable gold–sulfur (Au–S) bonds. The oriented immobilization led to reproducible surface-enhanced Raman spectroscopy (SERS) measurements of the reduced protein (RSD = 3.8%) and allowed for its direct electrochemical determination. After the SERS measurement, differential pulse voltammetry (DPV) was used to desorb the analyte from the substrate and generate a reduction current that is proportional to its concentration. CST-C was determined down to 1 pM and 62.5 nM by SERS and DPV, respectively, which satisfies the requirements for monitoring Alzheimer’s and kidney failure diseases. The new dual nanosensing methodology has strong potential for miniaturization in a lab-on-a-chip platform for the screening of many protein biomarkers that have a disulfide bond structure.

A label free electrochemical detection method for the rapid detection of recombinant human erythropoietin (rhuEPO) has been developed. In this method, we modified the rhuEPO structure for its direct sensing without using a complex signal amplification strategy. The protein was selectively extracted from blood plasma sample using target-specific magnetic beads. After releasing rhuEPO from the magnetic beads, its disulfide bonds were electrochemically reduced and the protein was spontaneously assembled onto a nanostructured gold electrode via Au-S bonds formation. For electrochemical quantification, the reduced protein was desorbed from the electrode surface using differential pulse voltammetry (DPV). The desorption current was proportional to the concentration of rhuEPO in the range 1 pM – 1000 pM. By cross-validating against ELISA, we found a 104.85 ± 3.35% agreement between the results obtained using the electrochemical biosensor and ELISA. Therefore the developed method has a strong potential for the sensitive detection of rhuEPO doping in sports as well as its rapid screening and pathology labs.

Poly sodium acrylate (PSA)-coated Magnetic Nanoparticles (PSA-MNPs) were synthesized as smart osmotic draw agent (SMDA) for water desalination by forward osmosis (FO) process. The PSA-coated MNPs demonstrated significantly higher osmotic pressure (~ 30 fold) as well as high FO water flux (~ 2–3 fold) when compared to their polymer (polyelectrolyte) counterpart, even at a very low concentration of ~ 0.13 wt.% in the draw solution. The PSA polymer chain conformation – coiled to extended – demonstrates a significant impact on the availability of the polymer hydrophilic groups in solution which is the driving force to attain higher osmotic pressure and water flux. When an optimum concentration of the polymer was anchored to a NP surface, the polymer chains assume an extended open conformation making the functional hydrophilic groups available to attract water molecules. This in turn boosts the osmotic pressure and FO water flux of the PSA-MNP draw agents. The low concentration of the PSA-MNP osmotic agent and the associated high water flux enhances the cost-effectiveness of our proposed SMDA system. In addition, easier magnetic separation and regeneration of the SMDA also improves its usability making it efficient, cost-effective and environment-friendly.

We report rapid and ultra-sensitive detection system for 2,4,6-trinitrotoluene (TNT) using unmodified gold nanoparticles and surface-enhanced Raman spectroscopy (SERS). First, Meisenheimer complex has been formed in aqueous solution between TNT and cysteamine in less than 15 min of mixing. The complex formation is confirmed by the development of a pink colour and a new UV-vis absorption band around 520 nm. Second, the developed Meisenheimer complex is spontaneously self-assembled onto unmodified gold nanoparticles through a stable Au-S bond between the cysteamine moiety and the gold surface. The developed mono layer of cysteamine-TNT is then screened by SERS to detect and quantify TNT. Our experimental results demonstrate that the SERS-based assay provide an ultra-sensitive approach for the detection of TNT down to 22.7 ng/L. The unambiguous fingerprint identification of TNT by SERS represents a key advantage for our proposed method. The new method provides high selectivity towards TNT over 2,4 DNT and picric acid. Therefore it satisfies the practical requirements for the rapid screening of TNT in real life samples where the interim 24-h average allowable concentration of TNT in waste water is 0.04 mg/L.

A facile and sensitive surface-enhanced Raman scattering substrate was prepared by controlled potentiostatic deposition of a closely packed single layer of gold nanostructures (AuNS) over a flat gold (pAu) platform. The nanometer scale inter-particle distance between the particles resulted in high population of ‘hot spots’ which enormously enhanced the scattered Raman photons. A renewed methodology was followed to precisely quantify the SERS substrate enhancement factor (SSEF) and it was estimated to be (2.2 ± 0.17) × 105. The reproducibility of the SERS signal acquired by the developed substrate was tested by establishing the relative standard deviation (RSD) of 150 repeated measurements from various locations on the substrate surface. A low RSD of 4.37 confirmed the homogeneity of the developed substrate. The sensitivity of pAu/AuNS was proven by determining 100 fM 2,4,6-trinitrotoluene (TNT) comfortably. As a proof of concept on the potential of the new pAu/AuNS substrate in field analysis, TNT in soil and water matrices was selectively detected after forming a Meisenheimer complex with cysteamine.

This communication presents a new pathway for the more precise quantification of surface-enhanced Raman scattering (SERS) enhancement factor via deducing resonance Raman scattering (RRS) effect from surface-enhanced resonance Raman scattering (SERRS). To achieve this, a self-assembled monolayer of 1,8,15,22-tetraaminophthalocyanatocobalt(II) (4α-CoIITAPc) is formed on plasmon inactive glassy carbon (GC) and plasmon active GC/AuNP surface. The surfaces are subsequently used as common probes for electrochemical and Raman (RRS and SERRS) studies. The most crucial parameters required for the quantification of SERS substrate enhancement factor (SSEF) such as real surface area of GC/AuNPs substarte and the number of 4α-CoIITAPc molecules contributing to RRS (on GC) and SERRS (on GC/AuNPs) are precisely estimated by cyclic voltammetry experiments. The present approach of SSEF quantification can be applied to varieties of surfaces by choosing an appropriate laser line and probe molecule for each surface. Keywords: Surface-enhanced Raman scattering (SERS), Electrochemistry and voltammetry, Nanoparticles, SERS substrate enhancement factor (SSEF), Quantification of SERS enhancement factor, 1,8,15,22-Tetraaminophthalocyanatocobalt(II)

We have explored the potential of deep Raman spectroscopy, specifically surface enhanced spatially offset Raman spectroscopy (SESORS), for non-invasive detection from within animal tissue, by employing SERS-barcoded nanoparticle (NP) assemblies as the diagnostic agent. This concept has been experimentally verified in a clinic-relevant backscattered Raman system with an excitation line of 785 nm under ex vivo conditions. We have shown that our SORS system, with a fixed offset of 2-3 mm, offered sensitive probing of injected QTH-barcoded NP assemblies through animal tissue containing both protein and lipid. In comparison to that of non-aggregated SERS-barcoded gold NPs, we have demonstrated that the tailored SERS-barcoded aggregated NP assemblies have significantly higher detection sensitivity. We report that these NP assemblies can be readily detected at depths of 7-8 mm from within animal proteinaceous tissue with high signal-to-noise (S/N) ratio. In addition they could also be detected from beneath 1-2 mm of animal tissue with high lipid content, which generally poses a challenge due to high absorption of lipids in the near-infrared region. We have also shown that the signal intensity and S/N ratio at a particular depth is a function of the SERS tag concentration used and that our SORS system has a QTH detection limit of 10-6 M. Higher detection depths may possibly be obtained with optimization of the NP assemblies, along with improvements in the instrumentation. Such NP assemblies offer prospects for in vivo, non-invasive detection of tumours along with scope for incorporation of drugs and their targeted and controlled release at tumour sites. These diagnostic agents combined with drug delivery systems could serve as a “theranostic agent”, an integration of diagnostics and therapeutics into a single platform.

Time‐resolved Raman spectroscopy, spatially offset Raman spectroscopy and time‐resolved spatially offset Raman spectroscopy (TR‐SORS) have proven their capability for the non‐invasive profiling of deep layers of a sample. Recent studies have indicated that TR‐SORS exhibits an enhanced selectivity toward the deep layers of a sample. However, the enhanced depth profiling efficiency of TR‐SORS, in comparison with time‐resolved Raman spectroscopy and spatially offset Raman spectroscopy, is yet to be assessed and explained in accordance to the synergistic effects of spatial and temporal resolutions. This study provides a critical investigation of the depth profiling efficiency of the three deep Raman techniques. The study compares the efficiency of the various deep Raman spectroscopy techniques for the stand‐off detection of explosive precursors hidden in highly fluorescing packaging. The study explains for the first time the synergistic effects of spatial and temporal resolutions in the deep Raman techniques and their impact on the acquired spectral data. Copyright © 2013 John Wiley & Sons, Ltd.

Current concerns regarding terrorism and international crime highlight the need for new techniques for detecting unknown and hazardous substances. A novel Raman spectroscopy-based technique, spatially offset Raman spectroscopy (SORS), was recently devised for non-invasively probing the contents of diffusely scattering and opaque containers. Here, we demonstrate a modified portable SORS sensor for detecting concealed substances in-field under different background lighting conditions. Samples including explosive precursors, drugs and an organophosphate insecticide (chemical warfare agent surrogate) were concealed inside diffusely scattering packaging including plastic, paper and cloth. Measurements were carried out under incandescent and fluorescent light as well as under daylight to assess the suitability of the probe for different real-life conditions. In each case, it was possible to identify the substances against their reference Raman spectra in less than one minute. The developed sensor has potential for rapid detection of concealed hazardous substances in airports, mail distribution centers and customs checkpoints.

Highlights - Combined extraction and detection of protein from biological fluid within the hour. - A highly efficient approach to the oriented immobilization of antibody fragments onto nanomaterial. - Facile recycle of functionalized nanoparticles for repeated extraction of biomolecules. - Facile synthesis of new paper-based substrate for cost effective SERS screening. - Highly portable rapid protein nanosensing methodology for biomedical and environmental applications. Abstract A highly sensitive nanosensing method for the combined selective capture and SERS detection of Microcystin-LR (MC-LR) in blood plasma has been developed. The new method utilizes gold coated magnetic nanoparticles that are functionalized with anti MC-LR antibody Fab' fragments for the selective capture of MC-LR from aqueous media and blood plasma. Using an oriented immobilization approach, the Fab' fragments are covalently attached to gold surface to form a monolayer with high capture efficiency towards the toxin. After the selective capture, the purified MC-LR molecules were released from the extractor nanoparticles within 5 min by manipulating the pH environment of the nanoparticles. The regenerated extractor nanoparticles maintained their capture efficiency and, therefore, were re-used to capture of MC-LR from successive samples. The released purified toxin was screened within 10 min on gold coated silicon nanopillars and a new paper-based SERS substrate by handheld Raman spectrometer. The SERS enhancement factors of the nanopillars and the new paper-based substrate were 2.5×106 and 3×105 respectively. The lower limit of quantification (LOQ) of MC-LR by SERS on the nanopillar substrate was 10 fM (R2=0.9975) which is well below the clinically required detection limit of the toxin. The SERS determination of MC-LR was cross validated against ELISA. By using antibody fragments that are specific to the target biomolecule, the new methodology can be extended to the rapid extraction and detection of other toxins and proteins.

We recently reported a polymer-coated magnetic nanoparticle (MNP) draw agent for the forward osmosis (FO) water desalination process. The water flux was found to increase when the polymer poly(sodium acrylate) (PSA) was anchored to the MNP surface as compared to the polymer (or polyelectrolyte solution) alone, due to the polymer chains being stretched out and most of the hydrophilic groups on the polymer contributing to water flux. We herein report the use of a secondary polymer poly(N-isopropylacrylamide) PNIPAM to manipulate the PSA polymer conformation and influence inter- and intrachain interactions to enhance the efficiency of the FO draw agent. These PSA-PNIPAM-coated MNPs generated a much higher water flux of ∼11.66 LMH when compared to the 100 % PSA-coated MNPs featuring a value of ∼5.32 LMH under identical FO conditions. The osmotic pressure and water flux driven by the mixed polymer-coated MNPs were found to be a strong function of the net polymer coverage on MNPs, that is, net available hydrophilic groups. Our new draw agent demonstrates potential for use in the water industry due to its improved efficiency and cost effectiveness as it uses only ∼0.062 % (w/v) of the draw agent solution.

Deep Raman spectroscopy has been utilized for the standoff detection of concealed chemical threat agents from a distance of 15 meters under real life background illumination conditions. By using combined time and space resolved measurements, various explosive precursors hidden in opaque plastic containers were identified non-invasively. Our results confirm that combined time and space resolved Raman spectroscopy leads to higher selectivity towards the sub-layer over the surface layer as well as enhanced rejection of fluorescence from the container surface when compared to standoff spatially offset Raman spectroscopy. Raman spectra that have minimal interference from the packaging material and good signal-to-noise ratio were acquired within 5 seconds of measurement time. A new combined time and space resolved Raman spectrometer has been designed with nanosecond laser excitation and gated detection, making it of lower cost and complexity than picosecond-based laboratory systems.

A time-resolved inverse spatially offset Raman spectrometer was constructed for depth profiling of Raman-active substances under both the lab and the field environments. The system operating principles and performance are discussed along with its advantages relative to traditional continuous wave spatially offset Raman spectrometer. The developed spectrometer uses a combination of space- and time-resolved detection in order to obtain high-quality Raman spectra from substances hidden behind coloured opaque surface layers, such as plastic and garments, with a single measurement. The time-gated spatially offset Raman spectrometer was successfully used to detect concealed explosives and drug precursors under incandescent and fluorescent background light as well as under daylight. The average screening time was 50 s per measurement. The excitation energy requirements were relatively low (20 mW) which makes the probe safe for screening hazardous substances. The unit has been designed with nanosecond laser excitation and gated detection, making it of lower cost and complexity than previous picosecond-based systems, to provide a functional platform for in-line or in-field sensing of chemical substances.

Spatially offset Raman spectroscopy (SORS) is a powerful new technique for the non-invasive detection and identification of concealed substances and drugs. Here, we demonstrate the SORS technique in several scenarios that are relevant to customs screening, postal screening, drug detection and forensics applications. The examples include analysis of a multi-layered postal package to identify a concealed substance; identification of an antibiotic capsule inside its plastic blister pack; analysis of an envelope containing a powder; and identification of a drug dissolved in a clear solvent, contained in a non-transparent plastic bottle. As well as providing practical examples of SORS, the results highlight several considerations regarding the use of SORS in the field, including the advantages of different analysis geometries and the ability to tailor instrument parameters and optics to suit different types of packages and samples. We also discuss the features and benefits of SORS in relation to existing Raman techniques, including confocal microscopy, wide area illumination and the conventional backscattered Raman spectroscopy. The results will contribute to the recognition of SORS as a promising method for the rapid, chemically specific analysis and detection of drugs and pharmaceuticals.

Modern detection and identification of chemical and biological hazards within the forensic and homeland security contexts may well require conducting the analysis in field while adapting a non-contact approach to the hazard. Technological achievements on both surface and resonance enhancement Raman scattering re-developed Raman spectroscopy to become the most adaptable spectroscopy technique for stand-off and non-contact analysis of hazards. On the other hand, spatially offset Raman spectroscopy proved to be very valuable for non-invasive chemical analysis of hazards concealed within non-transparent containers and packaging.

Molecular recognition of different enantiomers of a drug has become of increasing importance in the last decade due to the racemic switch strategy adapted by the pharmaceutical industry. Different analytical techniques to carry out enantioselective analysis of chiral compounds have been suggested in the literature. In the following, a brief overview of different techniques used for enantioselective analysis is given. Challenging aspects of these techniques, such as the quality of analytical information received from each technique, advantages, and disadvantages are discussed. Alternatives (enantioselective membranes, amperometric biosensors, molecularly imprinted polymers (MIPs)), capable of meeting the requirements of industrial processes, in terms of productivity, cost-effectiveness, and environmental issues are critically reviewed.

Erythropoietin (EPO), a glycoprotein hormone of ∼34 kDa, is an important hematopoietic growth factor, mainly produced in the kidney and controls the number of red blood cells circulating in the blood stream. Sensitive and rapid recombinant human EPO (rHuEPO) detection tools that improve on the current laborious EPO detection techniques are in high demand for both clinical and sports industry. A sensitive aptamer-functionalized biosensor (aptasensor) has been developed by controlled growth of gold nanostructures (AuNS) over a gold substrate (pAu/AuNS). The aptasensor selectively binds to rHuEPO and, therefore, was used to extract and detect the drug from horse plasma by surface enhanced Raman spectroscopy (SERS). Due to the nanogap separation between the nanostructures, the high population and distribution of hot spots on the pAu/AuNS substrate surface, strong signal enhancement was acquired. By using wide area illumination (WAI) setting for the Raman detection, a low RSD of 4.92% over 150 SERS measurements was achieved. The significant reproducibility of the new biosensor addresses the serious problem of SERS signal inconsistency that hampers the use of the technique in the field. The WAI setting is compatible with handheld Raman devices. Therefore, the new aptasensor can be used for the selective extraction of rHuEPO from biological fluids and subsequently screened with handheld Raman spectrometer for SERS based in-field protein detection. Electronic supplementary material The online version of this article (doi:10.1186/s12951-015-0102-8) contains supplementary material, which is available to authorized users.

Newly developed solid contact ion-selective electrodes (SC-ISE) have been proposed for determining diazepam, bromazepam and clonazepam 1,4-benzodiazepines in pure forms and in pharmaceutical preparations. The electrodes are based on polyvinylchloride (PVC) membranes doped with drug-tetraphenyl borate (TPB) or drug-phosphotungestic acid (PTA) ion pair complexes as electroactive materials. The new electrodes proved highly selective with selectivity coefficients ranging from 10 −4 to 10 −6 and detection limits ranging from 0.1 to 0.63g/ml. Successful application of developed electrodes for drugs determinations in pharmaceutical preparations was obtained. Calibration graphs were linear over the ranges of 0.29–71.20, 0.79–31.62 and 0.32–31.57g/ml for diazepam, bromazepam and clonazepam, respectively with slopes of 50–65 mV per decade in the optimum pH range of 4–7. Relative average errors ≤1.72% and relative standard deviations ≤1.13% were obtained. Statistical student’s t-test and F-test showed insignificant systematic error between measured and real values and also between developed ion-selective electrodes methods and a standard HPLC method. © 2003 Elsevier B.V. All rights reserved.

New, simple, low cost and sensitive ion-selective electrodes are described for the determination of some 1,4-benzodiazepines in their pharmaceutical preparations as well as in biological fluids. Drug-tetraphenylborate and drug-phosphotungstate ion pairs have been prepared and used as electroactive materials. Poly(vinyl chloride) (PVC), and poly(esterurethane)s (UPCLs, UPBA, and UPDEGA) are used as the matrix. The proposed sensors give rapid Nernstian responses for 10−4–10−6 M of the abovementioned drugs in a pH range of 3–7. The membranes developed have potential stability for up to 4 weeks and show high selectivity for the investigated drugs over many interfering ions. The electrodes are used for determining trace amounts of bromazepam, clonazepam and diazepam in their pharmaceutical preparations as well as in biological fluids. For pharmaceutical preparations, the relative standard deviation (RSD) values were in the range, 1.37–4.1, 0.7–2.52 and 0.3–1.2% for bromazepam, clonazepam and diazepam, respectively using the PVC based electrodes, while for the UPBA based electrodes, the (RSD) values were in the range 0.6–3.35, 0.7–2.45 and 0.6–2.41%. For biological samples, the RSD values were 0.64–1.88, 0.37–1.8 and 1.36–3.57% for bromazepam, clonazepam and diazepam, respectively. Comparison of the results obtained using the proposed electrodes with those found using a (HPLC) reference method showed that the ion-selective electrode technique is sensitive, reliable and can be used with very good accuracy and high % recovery without pretreatment procedures of the samples to minimize interfering matrix effects.