A Reliable Electrochemical Sensor Based on Functionalized Magnetite Nanoparticles for Over-the-counter Allergy Medication Abuse Sensing in Biological Fluids

Diphenhydramine (DIPH) has become one of the world‘s most widely abused over-the-counter medications. In addition to relieving allergy symptoms, it is also recognized for causing elevated energy and mild euphoric effects. The U.S. Food and Drug Administration (FDA) has recently warned about serious problems at high doses including heart problems, seizures, coma or even death among addicted teenagers. Herein, a simple, cost-effective, and reliable nanocomposite based electrochemical sensor was designed for DIPH quantification in biological fluids. Introducing the functionalized Fe₃O₄ nanoparticles (NPs) into the inner-filling solution and the PVC-based ion sensing membrane has been employed and compared to the classical potentiometric approach. The nanoparticles were incorporated to endorse in situ cooperative ion-pairing interaction between the ionophore and DIPH, and to improve the selectivity and detection limit (9.5×10⁻⁸ M). Nernstian potentiometric response was achieved for DIPH over the concentration range of 1.0×10⁻⁷ to 1.0×10⁻² M with a slope of 59.0±0.2 mV/decade. Inherent merits of the proposed sensor include fast response time (6 s), superior stability (60 days) with higher sensitivity and selectivity towards DIPH without interference from co-formulated drugs and several ions commonly found in biological matrices. The proposed sensor was successfully applied to the potentiometric determination of DIPH in different biological fluids (plasma and human milk) with an average recovery of 99.06±1.95 % and 100.34±1.92 %, respectively. As a consequence, the developed ISE might be the ideal choice for in-line DIPH measurements in plasma samples to identify overdose ingestion and its related symptoms, as well as for quality-control laboratories without prior treatments.     

Monitoring Imidazoline Derivatives via Functionalized Nano-Potentiometric Platforms in Aqueous Humor and Dosage Forms

The determination of two imidazoline derivatives [oxymetazoline HCl (OXY) and xylometazoline HCl (XYLO)] was described using different potentiometric platforms. The first electrode type was constructed using tetraphenyl borate (TPB) as anionic exchanger with β-cyclodextrins (β-CD) as ionophore forming oxymetazoline-tetraphenyl borate (OXY-TPB) and xylometazoline-tetraphenyl borate (XYLO-TPB), respectively. The second electrode type was prepared by modification of the first type by conjugation with magnetic iron oxide nanoparticles (MNP) forming (OXY-MNP) and (XYLO-MNP). The synthesized electrodes were fully characterized. The effect of magnetic nano-sized particles as a highly dispersible material with β-CDs on the electrode characteristics was investigated and compared against the classical electrodes. The response time, working pH range and selectivity coefficients were studied. The functionalized nano-electrodes (OXY-MNP and (XYLO-MNP) were found to be more sensitive than the classical electrodes with linearity ranges (1×10⁻⁶–1×10⁻² M). The functionalized nano-electrodes were successfully applied for the in-line analysis of OXY and XYLO in pharmaceutical dosage forms and spiked rabbit aqueous humor samples with no prior extraction of treatment. This suggests the future use of these electrodes in clinical studies of both drugs of interest.     

Synthesis and characterization of paramagnetic microparticles through emulsion-templated free radical polymerization

A novel method is described for the preparation of high-magnetization paramagnetic microparticles functionalized with a controlled density of poly(ethylene glycol) (PEG) and carboxyl groups. These microparticles were synthesized using four steps: (1) creation of an oil-in-water emulsion in which hydrophobic iron oxide nanoparticles and a UV-activated initiator were distributed in hexane; (2) formation of uniform microparticles through emulsion homogenization and evaporation of hexane; (3) functionalization of the microparticle with a PEG-functionalized surfactant and acrylic acid; and (4) polymerization of the microparticles. Characterization of the microparticles with electron microscopy and light scattering revealed that they were composed of densely packed iron oxide nanoparticles and that the size of the microparticles may be controlled through the pore size of the membrane used to homogenize the emulsion. The concentration of surfactant and acrylic acid used in the third processing step was found to determine the surface chemistry, iron content, and magnetization of the microparticles. Increasing the PEG surfactant to acrylic acid ratio resulted in higher PEG surface densities, lower iron content, and lower magnetization. The resulting microparticles were readily functionalized with antibodies and showed a low propensity for nonspecific protein adsorption. We believe that these microparticles will be useful for magnetic tweezers measurements and bioanalytical devices that require microparticles with a high magnetization.     

Non-covalently functionalized graphene for the potentiometric sensing of zinc ions

The possibility of the application of non-covalently functionalized graphene as a sensing membrane for the potentiometric determination of zinc ions was examined. A graphene carboxylic derivative was functionalized with 1-(2-pyridylazo)-2-naphthol, the Zn(2+) ions complexing ligand, simply by adsorption of ligand molecules due to π-π interactions. This approach has resulted in a potentiometric sensor characterized with significant selectivity for Zn(2+) ions present in solution.     

Potentiometric detection of polyions based on functionalized magnetic nanoparticles

A novel potentiometric detection strategy based on functionalized magnetic nanoparticles has been developed for rapid and sensitive sensing of polyions. Highly dispersed magnetic nanoparticles coated with ion exchanger and plasticizer could promote an in situ cooperative ion-pairing interaction between the ion exchanger and the polyion analyte in sample solution by dramatically reducing the mass-transfer distance. With applying a magnetic field, the nanoparticles can be attached to the surface of ion exchanger free polymeric membrane. The observed potential signals are related to the polyion concentrations. The proposed polymeric membrane electrode exhibits a linear relationship between the greatest potential response slope (dE/dt) and the logarithm of protamine concentration in the range of 0.05−5 μg/mL with a lower detection limit of 0.033 μg/mL.     

Solid-contact potentiometric sensor for ascorbic acid based on cobalt phthalocyanine nanoparticles as ionophore

A novel solid-contact potentiometric sensor for ascorbic acid based on cobalt phthalocyanine nanoparticles (NanoCoPc) as ionophore was fabricated without any need of auxiliary materials (such as membrane matrix, plasticizer, and other additives). The electrode was prepared by simple drop-coating NanoCoPc colloid on the surface of a glassy carbon electrode. A smooth, bright and blue thin film was strongly attached on the surface of the glassy carbon electrode. The electrode showed high selectivity for ascorbic acid, as compared with many common anions. The influences of the amount of NanoCoPc at the electrode surface and pH on the response characteristics of the electrode were investigated. To overcome the instability of the formal potential of the coated wire electrode, a novel electrochemical pretreatment method was proposed for the potentiometric sensor based on redox mechanism. This resulting sensor demonstrates potentiometric response over a wide linear range of ascorbic acid concentration (5.5 × 10⁻⁷ to 5.5 × 10⁻² M) with a fast response (<15 s), lower detection limit (ca. 1.0 × 10⁻⁷ M), and a long-term stability. Furthermore, microsensors based on different conductors (carbon fiber and Cu wire) were also successfully fabricated for the determination of practical samples.     

Highly sensitive and selective solid-contact calcium sensor based on Schiff base of benzil with 3-aminosalycilic acid covalently attached to polyacrylic acid amide for health care

Solid-state potentiometric calcium sensors based on newly synthesized Schiff’s base of 3-aminosalycilic acid with benzil [2-hydroxy-3-(2-oxo-1,2-diphenylethylidene)amino) benzoic acid] ionophore I and with isatin [2-hydroxy-3-(2-oxoindolin-3-ylidene amino)benzoic acid] ionophore II ionophores and their covalently attached to polyacrylamide ionophores III and IV, respectively, were developed. The all-solid-state sensors were constructed by the application of a thin film of polymeric membrane cocktail onto gold electrodes that were pre-coated with the conducting polymer poly (3,4-ethylenedioxy-thiophen) as an ion and electron transducer. More than 40 sensors with membranes containing plasticized PVC or poly(butyl methacrylate-co-dodecyl methacrylate as a plasticizer-free membrane matrix were investigated. The constructed sensors contained various amounts of the different ionophores with and without anionic lipophilic additive. The sensor containing 10% of ionophore III and 3% tetra (p-chlorophenyl) borate in acrylate copolymer exhibited a stable potentiometric response over a wide pH range of 4–9. It possessed a linear concentration range of 6 10^?10 to 1 10^?2 mol L^?1 with a Nernstian slope of 28.5 mV/decade and a limit of detection (LOD) of 2 10^?10 mol L^?1. It exhibited a good selectivity for calcium to other cations. The selectivity coefficients towards different mono-, di- and trivalent cations were determined with the fixed interference method (FIM) and separate solution method (SSM). The sensor’s life time is more than 3 months, without significant deterioration in the slope. The proposed sensors were utilized for the determination of calcium concentration in serum. The results were compared with those obtained from routine clinical laboratory electrolyte analyser. The results reveal that the all-solid-state calcium sensor is promising for the point of care testing.     

Potentiometric and theoretical studies of the carbonate sensors based on 3-bromo-4-hexyl-5-nitrotrifluoroacetophenone

Novel carbonate ionophore, trifluoroacetophenone derivative (TFA) substituted by two acceptor substituents in the phenyl ring (3-bromo-4-hexyl-5-nitrotrifluoroacetophenone), was synthesized. Solvent polymeric membrane sensors based on this ionophore exhibited heightened selectivity to carbonate ions in the presence of the most important interfering anions. A wide range of potentiometric properties were studied and compared with those of sensors based on mono-substituted ionophores. Special attention was paid to pH dependence of sensor responses and to elaboration of appropriate conditions for carbonate analysis. A segmented-sandwich membrane method was applied for determination of the stoichiometry of ionophore-carbonate complexes, which was determined to be 1:3, and apparent complex formation constants which were 14.4 and 13.6 for DOS- and NPOE-plasticized membranes, respectively. Theoretical studies on TFA derivatives by semi-empirical (AM1 and PM3) and ab initio(6-31+G*) methods were performed, considering different types of possible ionophore-ion interactions. The formation of hydrogen bonds between carbonate and hydrated TFA was proved to be much more favourable in terms of energy compared to tetrahedral nucleophilic adducts that earlier were postulated to being formed in the membrane phase. The final conclusion on the mechanism of carbonate sensing by TFA-based solvent polymeric membrane sensors was made on the basis of computational data and detailed analysis of the literature.     

Novel potentiometric membrane sensor for the determination of trace amounts of chromium(III) ions.

A plasticized Cr3+ ion sensor by incorporating 2,3,8,9-tetraphenyl-1,4,7,10-tetraazacyclododeca-1,3,7,9-tetraene (TTCT) ionophore exhibits a good potentiometric response for Cr3+ over a wide concentration range (1.0 x 10(-6)-1.0 x 10(-1) M) with a slope of 19.5 mV per decade. The sensor response is stable for at least three months. Good selectivity for Cr3+ in comparison with alkali, alkaline earth, transition and heavy metal ions, and minimal interference are caused by Li+, Na+, K+, Co2+, Hg2+, Ca2+, Pb2+ and Zn2+ ions, which are known to interfere with other chromium membrane sensors. The TTCT-based electrode shows a fast response time (15 s), and can be used in aqueous solutions of pH 3-5.5. The proposed sensor was used for the potentiometric titration of Cr3+ with EDTA and for a direct potentiometric determination of Cr3+ content in environmental samples.     

Fabrication of novel coated pyrolytic graphite electrodes for the selective nano-level monitoring of Cd ions in biological and environmental samples using polymeric membrane of newly synthesized macrocycle

Novel 5-amino-1,3,4-thiadiazole-2-thiol unit based macrocyclic ionophore 5,11,17-trithia-1,3,7,9,13,15,19,20,21-nonaazatetracyclo[14.2.1.1^4,7.1^10,13]henicosa-4(20),10(21),16(19)-triene-6,12,18-trithione (M₁), was synthesized and characterized. Preliminary studies on M₁ have showed that it has more the affinity toward Cd²⁺ ion. Thus, the macrocyclic ionophore (M₁) was used as electroactive material in the fabrication of PVC-membrane electrodes such as polymeric membrane electrode (PME), coated graphite electrode (CGE) and coated pyrolytic graphite electrode (CPGE) were prepared and its performance characteristic were compared with. The electroanalytical studies performed on PME, CGE and CPGE revealed that CPGE having membrane composition M₁:PVC:1-CN:NaTPB in the ratio of 7:37:54:2 exhibits the best potentiometric characteristics in terms of detection limit of 7.58 × 10⁻⁹ mol L⁻¹, Nernstian slope of 29.6 mV decade⁻¹ of activity. The sensor was found to be independent of pH in the range 2.5–8.5. The sensor showed a fast response time of 10 s and could be used over a period of 4 months without any significant divergence in its potentiometric characteristics. The sensor has been employed for monitoring of the Cd²⁺ ion in real samples and also used as an indicator electrode in the potentiometric titration of Cd²⁺ ion with EDTA.     

Development of All‐solid‐state Antidiabetic Drug Metformin‐selective Microsensor and its Electrochemical Applications

In this study, all‐solid‐state type potentiometric PVC membrane selective microsensor was developed for Metformin (MET) which is an antidiabetic drug active substance. Metformin‐tetraphenylborate (MET‐TPB) ion‐pair was used as an ionophore in the structure of the sensor membrane. It was determined that the sensor membrane at the ratio of 69 % o‐nitrophenyl octyl ether, 27 % polyvinyl chloride and 4 % MET‐TPB performed the best potentiometric performance. In a wide concentration range (1×10^?5–1×10^?1 mol/L), the slope, detection limit, response time, pH range, and life‐time of the sensor were determined as 55.9±1.6 mV (R²=0.996), 3.35×10^?6 mol/L, 8–10 s, pH: 3–8, and ～10 weeks, respectively. The voltammetric performances of the sensor were also investigated. The prepared microsensor was successfully utilized for the determination of Metformin in a pharmaceutical drug sample by potentiometry and voltammetry. It was observed that the obtained results were in agreement with the results obtained by the UV spectroscopy method at 95 % confidence level.     

Lead(II) ion-selective electrode based on polyaminoanthraquinone particles with intrinsic conductivity

A new polyvinylchloride membrane electrode was facilely prepared by using polyaminoanthraquinone (PAAQ) microparticles with an intrinsically electrical conductivity as a lead(II) ionophore. It is found that the electrode performance will significantly be improved with adding 1 wt% PAAQ microparticles and decreasing the membrane thickness. A 90 μm-thick membrane electrode consisting of PAAQ(salt):polyvinyl chloride:dioctylphthalate:sodium tetraphenylborate of 1:33:66:1 (wt) but without any traditional lead(II) ionophore achieved the optimal performance and exhibited a good Nernstian response for Pb(II) ions over a wide concentration range from 2.5 × 10⁻⁶ to 0.1 M with a slope of 28.9 mV/decade and a detection limit down to 776 nM. A reasonably short response time of 12 s was revealed together with a long lifetime over a period of around 4 months in a wide pH range between 2.8 and 5.2. A fixed interference method indicated that the electrode has an excellent selectivity for lead(II) ion over alkali, alkaline earth and other heavy metal ions. The proposed electrode has been also found to be a powerful indicator electrode for potentiometric titration of Pb(II) ions with EDTA. The electrode can be used to accurately monitor the Pb(II) pollution in environmental waters.     

The first use of a Rh(III) complex as a novel ionophore for thiocyanate-selective polymeric membrane electrodes

The feasibility of a newly synthesized Rh(III) complex, Rh[(trpy)(bpy)Cl](PF₆)₂, as a novel ionophore for the preparation of anion-selective polymeric membrane electrodes was tested. The ionophore exhibited anti-Hofmeister behavior with enhanced potentiometric selectivity toward thiocyanate ion compared to other anions. The influence of some experimental parameters such as membrane composition, nature and amount of plasticizer and additive and concentration of internal solution on the potential response of the SCN⁻ sensor were investigated. The electrode exhibits a Nernstian response for SCN⁻ over a wide concentration range (1.0 × 10⁻⁵ to 1.0 × 10⁻¹ M) with a slope −58.7 ± 0.5 mV per decade and a detection limit of 4.0 × 10⁻⁶ M (0.23 ppm). It could be used in a pH range of 3.0-8.0 and has a fast response time of about 15 s. The proposed sensor was used for the determination of thiocyanate ions in real samples such as urine and saliva of smokers and nonsmokers and, as an indicator electrode, in potentiometric titrations of SCN⁻ ion.     

A photo-cured coated-wire calcium ion selective electrode for use in flow injection potentiometry

A multi-sensor cell containing a new photo-cured calcium ion selective electrode sensor is reported. Four membranes containing different components are prepared to determine the one with optimum selectivity and sensitivity. This is shown to consist of the N,N,N',N'-tetracyclohexyl-3-oxapentanediamide ligand (ETH 129) as the ionophore, 2-nitrophenyl octyl ether as the plasticiser and tetradodecyl ammonium tetrakis(4-chlorophenyl) borate as the lipophilic additive. The photo-curing process is applied after coating a thin membrane on a silver wire as substrate transducer to produce the calcium sensor. The curing process is demonstrated to be faster (1 min) than previous methods and does not require a nitrogen atmosphere for reproducible production of membrane response characteristics. Four sensors constructed with the identical optimum membrane are shown to function reproducibly in a multi-sensor flow-through cell using the steady-state mode of flow measurement, and an average calibration slope of 28.5+/-0.4 mV change per activity decade is observed over a log-linear concentration range between 0.01 and 10 mM. The sensor is also shown to respond to changes in pH. Hence, in the flow injection potentiometric mode, a constant carrier buffer composition of pH 8.3 is required for accurate potentiometric calcium determinations. The sensor is used to determine calcium in water samples by flow injection potentiometry. The accuracy of the electrode determination relative to atomic absorption spectroscopy was in the range 5-9% for three different water samples.     

Tetrakis(4-N,N-dimethylaminobenzene)porphyrinato]manganese(III) acetate as a novel carrier for a selective iodide PVC membrane electrode.

[5,10,15,20-Tetrakis(4-N,N-dimethylaminobenzene)porphyrinato]Mn(III) acetate (MnTDPAc) was applied as an ionophore for an iodide-selective PVC membrane electrode. The influences of the membrane composition, pH of the test solution and foreign ions on the electrode performance were investigated. The sensor exhibited not only excellent selectivity to iodide ion compared to Cl- and lipophilic anions such as ClO4- and salicylate, but also a Nernstian response with a slope of -59.4 +/- 1.2 mV per decade for iodide ions over a wide concentration range from 1.0 x 10(-2) to 7.5 x 10(-6) M at 25 degrees C. The potentiometric response was independent of the pH of the solution in the pH range of 2 - 8. The electrode could be used for at least 2 months without any considerable divergence in the potential. Good selectivity for iodide ion, a very short response time, simple preparation and relatively long-term stability were the silent characteristics of this electrode. It was successfully used as an indicator electrode in the potentiometric titration of iodide ions, and also in the determination of iodide from seawater samples and drug formulations.     

Ribonucleic acid as a novel ionophore for potentiometric membrane sensors of some transition metal ions

Ribonucleic acid (RNA) is used as a novel ionophore in plasticized poly(vinyl chloride) matrix membrane sensors for some transition metal ions. Membranes incorporating RNA and doped in Cu(2+), Cd(2+) and Fe(2+) display fast near-Nernstian and stable responses for these ions with cationic slopes of 31.1, 31.3 and 35.5 mV per decade, respectively, over the concentration range 10(-6)-10(-2) M and pH range 4-6.5. The cadmium RNA-based sensor shows no interference by Cu(2+), Fe(2+) Hg(2+) and Ag(+), which are known to interfere significantly with the solid-state CdS/Ag(2)S membrane electrode. The copper RNA-based sensor displays general potentiometric characteristics similar to those based on macrocyclic ionophores and organic ion exchangers and has the advantage of a better selectivity for Cu(2+) over some alkaline earth, divalent and transition metal ions. The iron RNA-based membrane sensor exhibits no interference by Hg(2+) and Zn(2+), which are known to interfere with other previously suggested sensors. The nature and composition of the RNA ionophore and its cadmium complex are examined using electrophoresis, Fourier-transform infrared analysis, elemental analysis and X-ray fluorescence techniques.     

A Renewable Potentiometric Immunosensor Based on Fe3O4 Nanoparticles Immobilized Anti‐IgG

A renewable potentiometric immunosensor for detection of immunoglobulin G (IgG) has been developed by magnetic force attraction of Fe₃O₄ nanoparticles immobilized goat‐anti‐human IgG antibody. For preparing sensitive film of the sensor, cysteine was bonded on the nano‐Fe₃O₄ particles surface. The cysteine functionalized magnetic nanoparticles was attracted on a solid paraffin carbon paste electrode surface to covalently immobilize of anti‐immunoglobulin G (anti‐IgG) by employing a conventional glutaraldehyde‐crosslinking method. The immunosensor showed a specific response to human immunoglobulin G in the range of 0.1–1.2 ng/mL with a detection limit of 0.023 ng/mL. The immunosensor based on the magnetic nanoparticles was made easily by this method. It can be used expediently, renewed easily and low‐cost relatively. The renewable potentiometric immunosensor with better stability and higher sensitivity can be employed extensively in clinical diagnosis, monitoring of disease and environmental studies and etc.     

Solid-contact ionophore-based electrode for determination of pH in acidic media

Solid-contact electrode for pH measurements in acidic media is described. The sensor membrane is made of polyvinyl chloride plasticized with bis(2-ethylhexyl)phthalate and contains neutral pH-selective ionophore hexabutyltriamidophosphate and potassium tetrakis-p-Cl-phenylborate cation exchanger. The transducer layer of the solid-contact electrode contains the same membrane composition and also carbon black and electron–ion-exchanger resin EI-21(a cation exchange resin containing fine dispersion of metal copper) for stabilization of the electrode potential. The electrode is suitable for measurements of pH in the range 0–6 and works also in hydrofluoric acid (HF) solutions up to 0.1 M HF. Chronopotentiometric measurements show diffusion-limited polarization at the interface between sensor membrane and transducer layer. The slope of the linearized polarization curve correlates with the long-term stability of the electrode potentials providing a tool for prediction of the long-term stability of solid-contact potentiometric sensors.     

Mass spectrometry signal amplification for ultrasensitive glycoprotein detection using gold nanoparticle as mass tag combined with boronic acid based isolation strategy

We describe a novel method for rapid and ultrasensitive detection of intact glycoproteins without enzymatic pretreatment which was commonly used in proteomic research. This method is based on using gold nanoparticle (AuNP) as signal tag in laser desorption/ionization mass spectrometry (LDI-MS) analysis combined with boronic acid assisted isolation strategy. Briefly speaking, target glycoproteins were firstly isolated from sample solution with boronic acid functionalized magnetic microparticles, and then the surface modified gold nanoparticles were added to covalently bind to the glycoproteins. After that, these AuNP tagged glycoproteins were eluted from magnetic microparticles and applied to LDI-MS analysis. The mass signal of AuNP rather than that of glycoprotein was detected and recorded in this strategy. Through data processing of different standard glycoproteins, we have demonstrated that the signal of AuNP could be used to quantitatively represent glycoprotein. This method allows femtomolar detection of intact glycoproteins. We believe that the successful validation of this method on three different kinds of glycoproteins suggests the potential use for tracking trace amount of target glycoproteins in real biological samples in the near future.     

Room Temperature Ionic Liquids (RTILs) and Multiwalled Carbon Nanotubes (MWCNTs) as Modifiers for Improvement of Carbon Paste Ion Selective Electrode Response; A Comparison Study with PVC Membrane

Room temperature ionic liquids (RTILs), 1‐n‐butyl‐3‐methylimidazolium tetrafluoroborate, [bmim]BF₄, and multiwalled carbon nanotubes (MWCNTs) were used for improvement of a praseodymium carbon paste ion selective sensor response. [bmim]BF₄ can be a better binder than mineral oils. MWCNTs have a good conductivity which helps the transduction of the signal in carbon paste electrode. The characteristics of these electrodes as potentiometric sensors were evaluated and compared with PVC membrane sensor. The results indicate that potentiometric sensor constructed with ionic liquid shows an increase in performance in terms of Nernstian slope, selectivity, response time, and response stability compared to Pr(III) PVC membrane sensor.