Chemical Sensors Based on Molecularly Imprinted Polymers Can Determine Drug Release Kinetics from Nanocarriers without Filtration, Centrifugation, and Dialysis Steps.

With the development of drug delivery systems, the use of nanomaterials for slow, targeted, and effective drug release has grown significantly. To ensure the quality of performance, it is essential to obtain drug release profiles from therapeutic nanoparticles prior to in vivo testing. Typically, the methods of monitoring the drug release profile from nanoparticle drug delivery systems include one or more filtration, separation, and sampling steps, with or without membrane, which cause several systematic errors and make the process time-consuming. Here, the release rate of doxorubicin as a model drug from liposome as a nanocarrier was determined via highly selective binding of released doxorubicin to the doxorubicin-imprinted electropolymerized polypyrrole as a molecularly imprinted polymer (MIP). Incubation of the MIP-modified substrate with imprinted cavities complementary to doxorubicin molecules in the releasing medium leads to the binding of released doxorubicin molecules to cavities. The drug trapped in the cavities is determined by one of the analytical methods depending on its signaling properties. In this work, due to the favorable electrochemical properties of doxorubicin, the voltammetry method was used for quantitative analysis of released doxorubicin. The voltammetric oxidation peak current intensity of doxorubicin on the surface of the electrode was enhanced by increasing the release time. This membranelle platform allows fast, reliable, and simple monitoring of drug release profiles without any sample preparation, filtration, and centrifugation in buffer and blood serum samples.

Mediator-Free Self-Powered Bioassay for Wide-Range Detection of Dissolved Carbon Dioxide.

Electrochemical sensors for the dissolved CO2 (dCO2) measurement have attracted great interest because of their simple setup and the resulting low costs. However, the developed sensors suffer from the requirement of the external electrical power supply throughout the sensing. Here, the fabrication and evaluation of a self-powered biosensor based on biofuel cells (BFCs) for dCO2 measurements are described. In this device, AuNPs-multiwalled carbon nanotubes/GOx-modified carbon paper (CP) served as a bioanode for the oxidation of glucose, while imine-linked covalent triazine framework (I-CTF)-modified CP was employed as the cathode for the reduction of Fe(CN)63-. I-CTF is a porous organic polymer with a high CO2 capture capacity. Voltammetry and electrochemical impedance spectroscopy confirmed that the electron transfer of Fe(CN)63- on the I-CTF-modified electrode decreases after contacting I-CTF with dCO2. In the designed BFC, by capturing CO2 by the I-CTF-modified cathode, a significant decrease in open-circuit voltage (EOCV) of the BFC was observed, which can be used for the sensitive measurement of dCO2. In addition to the self-powering feature, the EOCV of the BFC sensor can be restored when the captured CO2 is desorbed from the I-CTF-modified cathode by increasing the temperature of the cathode. Finally, the BFC is integrated into a circuit containing a matching capacitor; the charges generated by the BFC are accumulated on the capacitor, and then the instantaneous current is quickly detected using a switching regulator and a digital multimeter. Under optimal conditions, the instantaneous current of the BFC sensor was found to sensitively respond to dCO2 in a wide concentration range from 1.3 × 10-5 to 0.252 atm with a low detection limit of 5 × 10-6 atm.

A novel aptasensing method for detecting bisphenol A using the catalytic effect of the Fe3O4/Au nanoparticles on the reduction reaction of the silver ions.

The gold electrode was functionalized with anti-bisphenol A (BPA) aptamer and captured the BPA as analyte. By dropping the aptamer-modified magnetic Fe3O4/Au nanoparticles solution onto the electrode, a BPA molecule attaches to many aptamers that are in contact with a large number of Fe3O4/Au nanoparticles. The modified electrode were transferred to a solution containing Ag+ ions. Fe3O4/Au nanoparticles reduce the Ag+ ions to Ag0. A potential scan was applied for the oxidation of the Ag0-loaded magnetic nanoparticles to the AgCl. The magnitude of the stripping anodic signal of the Ag0 was related to the concentration of the BPA. The assay shows a detection limit of 0.6 fmol L-1 and linear range of 1 fmol L-1-150 pmol L-1 and. The applicability of the aptasensor is measured by its successful use in the sensing BPA in water, milk and juice samples and measuring BPA migration from different commercial plastic products.

Efficient immobilization of aptamers on the layered double hydroxide nanohybrids for the electrochemical proteins detection.

Despite the use of layered double hydroxides (LDH) in different electrochemical (bio)sensors, the construction of aptasensors using LDH-based surfaces was not reported to the best of our knowledge. This may be due to the lack of a suitable linker to attach aptamers to the LDH-modified surface. LDH-based aptasensors are established here as very sensitive and reliable devices in serum and cerebrospinal fluid (CSF) analysis. 5'-NH2 DNA aptamer probes were immobilized on the LDH-based surfaces in a vertical conformation without any linker materials. Due to the low electron conductivity of the LDH, carbon nanotubes (CNT) with high electronic conductivity and high surface area were combined with LDH. Thrombin was used as a model protein for aptasensing. The sensor shows a linear range of 0.005-12,000 pmol L-1 and a limit of detection of 0.1 fmol L-1. Moreover, the aptasensor was used for the sensing of thrombin in CSF and serum samples acquired from both healthy and patients with different disease.

Impedimetric aptasensing of the breast cancer biomarker HER2 using a glassy carbon electrode modified with gold nanoparticles in a composite consisting of electrochemically reduced graphene oxide and single-walled carbon nanotubes.

A method is presented for electrochemical determination of the breast cancer biomarker HER2. A glassy carbon electrode (GCE) was modified with densely packed gold nanoparticles placed on a composite consisting of electrochemically reduced graphene oxide and single walled carbon nanotubes (ErGO-SWCNTs). An aptamer directed against HER2 was then immobilized ono the GCE. The modified GCE was characterized by cyclic voltammetry, differential pulse voltammetry and electrochemical impedance spectroscopy. The immobilized aptamer selectively recognizes HER2 on the electrode interface, and this leads to an increased charge transfer resistance (Rct) of the electrode when using ferri/ferro-cyanide as the electrochemical probe. The method has a low limit of detection (50 fg·mL-1) and a wide analytical range (0.1 pg·mL-1 to 1 ng·mL-1). The assay is highly reproducible and specific. Clinical application was demonstrated by analysis of the HER2 levels in serum samples, and sera of breast cancer patients were successfully discriminated from sera of healthy persons. Graphical abstract An electrochemical aptasensor for HER2 is described that is based on the immobilization of anti-HER2 aptamer on a glassy carbon electrode modified with a nanocomposite prepred fromreduced graphene oxide, carbon nanotubes and gold nanoparticles.

A glassy carbon electrode modified with TiO2(200)-rGO hybrid nanosheets for aptamer based impedimetric determination of the prostate specific antigen.

TiO2(200)-rGO hybrid nanosheets were synthesized starting from TiO2, rGO and NaOH solid powders via a scalable hydrothermal process. The weight ratio of TiO2-GO was found to be crucial on the crystal growth and biosensor properties of the final hybrid nanosheets. They were characterized by means of SEM, FESEM-EDX, XRD, XPS, Raman and FTIR spectroscopies in order to verify the formation of very thin TiO2 anatase nanosheets with an orientation of the anatase crystal structure towards the (200) plane. The free active sites of TiO2 structure and the large surface of the 2D graphene structure strongly facilitate charge transport confirmed by BET-BJH analyses. Compared to pure AuNPs, rGO and TiO2, the hybrid nanosheet modified electrode represents the most sensitive aptasensing platform for the determination of PSA. The detection was based on that the variation of electron transfer resistance (Rct) at the modified electrode surface in a solution containing 3.0 mmol L-1 [Fe(CN)6]3-/4- as a redox probe and 0.1 mol L-1 KCl as supporting electrolyte. The detection limit of the sensor is 1 pg mL-1, and the sensor can be operated up to 30 days. It was applied to the analysis of PSA levels in spiked serum samples obtained from patients with prostate cancer. Data compare well with those obtained by an immunoradiometric assay. Graphical abstract Scalable reduced graphene oxide (rGO)-TiO2(200) mesoporous hybrid nanosheets with large surface area and new crystal growth of anatase (A) are introduced as efficient, durable, selective with low detection limit aptamer based prostate specific antigen biosensor.

Electrochemical bioassay development for ultrasensitive aptasensing of prostate specific antigen.

A densely packed gold nanoparticles on the rGO-MWCNT platform was used as the basis for an ultrasensitive label-free electrochemical aptasensor to detect the biomarker prostate specific antigen (PSA) in serum. The detection was based on that the variation of electron transfer resistance (Rct) and differential pulse voltammetry (DPV) current were relevant to the formation of PSA-aptamer complex at the modified electrode surface. Compared with pure AuNPs, rGO-MWCNT and MWCNT/AuNPs, the rGO-MWCNT/AuNPs nanocomposite modified electrode was the most sensitive aptasensing platform for the determination of PSA. Two calibration curves were prepared from the data obtained from the DPV and electrochemical impedance spectroscopy (EIS) by plotting the peak current and Rct against PSA concentration, respectively. The proposed aptasensor had an extremely low LOD of 1.0pgmL-1 PSA within the detection range of 0.005-20ngmL-1 and 0.005-100ngmL-1 for DPV and EIS calibration curves, respectively. This sensor exhibited outstanding anti-interference ability towards co-existing molecules with good stability, sensitivity, and reproducibility. Clinical application was performed with analysis of the PSA levels in serum samples obtained from patients with prostate cancer using both the aptasensor and Immunoradiometric assay. The results revealed the proposed system to be a promising candidate for clinical analysis of PSA.

An electrochemical aptasensor based on TiO2/MWCNT and a novel synthesized Schiff base nanocomposite for the ultrasensitive detection of thrombin.

A sensitive aptasensor based on a robust nanocomposite of titanium dioxide nanoparticles, multiwalled carbon nanotubes (MWCNT), chitosan and a novel synthesized Schiff base (SB) (TiO2/MWCNT/CHIT/SB) on the surface of a glassy carbon electrode (GCE) was developed for thrombin detection. The resultant nanocomposite can provide a large surface area, excellent electrocatalytic activity, and high stability, which would improve immobilization sites for biological molecules, allow remarkable amplification of the electrochemical signal and contribute to improved sensitivity. Thrombin aptamers were simply immobilized onto the TiO2-MWCNT/CHIT-SB nanocomposite matrix through simple π - π stacking and electrostatic interactions between CHIT/SB and aptamer strands. The electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV) and differential pulse voltammetry (DPV) were used to analyze the surface characterization of unmodified GCE and TiO2-MWCNT/CHIT-SB modified GCE, and also the interaction between aptamer and thrombin. In the presence of thrombin, the aptamer on the adsorbent layer captures the target on the electrode interface, which makes a barrier for electrons and inhibits electron transfer, thereby resulting in decreased DPV and increased impedance signals of the TiO2-MWCNT/CHIT-SB modified GCE. Furthermore, the proposed aptasensor has a very low LOD of 1.0fmolL(-1) thrombin within the detection range of 0.00005-10nmolL(-1). The aptasensor also presents high specificity and reproducibility for thrombin, which is unaffected by the coexistence of other proteins. Clinical application was performed with analysis of the thrombin levels in blood and CSF samples obtained from patients with MS, Parkinson, Epilepsy and Polyneuropathy using both the aptasensor and commercial ELISA kit. The results revealed the proposed system to be a promising candidate for clinical analysis of thrombin.

Electrochemical study of quinone redox cycling: A novel application of DNA-based biosensors for monitoring biochemical reactions.

This paper presents the results of an experimental investigation of voltammetric and impedimetric DNA-based biosensors for monitoring biological and chemical redox cycling reactions involving free radical intermediates. The concept is based on associating the amounts of radicals generated with the electrochemical signals produced, using differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS). For this purpose, a pencil graphite electrode (PGE) modified with multiwall carbon nanotubes and poly-diallydimethlammonium chloride decorated with double stranded fish sperm DNA was prepared to detect DNA damage induced by the radicals generated from a redox cycling quinone (i.e., menadione (MD; 2-methyl-1,4-naphthoquinone)). Menadione was employed as a model compound to study the redox cycling of quinones. A direct relationship was found between free radical production and DNA damage. The relationship between MD-induced DNA damage and free radical generation was investigated in an attempt to identify the possible mechanism(s) involved in the action of MD. Results showed that DPV and EIS were appropriate, simple and inexpensive techniques for the quantitative and qualitative comparisons of different reducing reagents. These techniques may be recommended for monitoring DNA damages and investigating the mechanisms involved in the production of redox cycling compounds.

Determination of atropine sulfate using a novel sensitive DNA-biosensor based on its interaction on a modified pencil graphite electrode.

A novel, selective, rapid and simple electrochemical method is developed for the determination of atropine sulfate. UV-Vis and differential pulse voltammetry are used to study the interaction of atropine sulfate with salmon sperm ds-DNA on the surface of salmon sperm ds-DNA modified-pencil graphite electrode (PGE). For this purpose, a pencil graphite electrode (PGE) modified with multiwall carbon nanotubes (MWCNTs), titanium dioxide nanoparticles (TiO2NPs), and poly-dialyldimethylammonium chloride (PDDA) decorated with ds-DNA is tested for the determination of atropine sulfate. The electrochemical oxidation peak current of adenine and guanine bonded on the surface of ds-DNA/PDDA-TiO2NPs-MWCNTs/PGE is used to obtain the analytical signal. Decreases in the intensities of guanine and adenine oxidation signals after their interaction with atropine sulfate are used as indicator signals for the sensitive determination of atropine sulfate. Using ds-DNA/PDDA-TiO2NPs-MWCNTs/PGE and based on the guanine signal, linear calibration curves were obtained in the range of 0.6 to 30.0 µmol L(-1) and 30.0 to 600.0 µmol L(-1) atropine sulfate with low detection limits of 30.0 nmol L(-1). The biosensor shows a good selectivity for the determination of atropine sulfate. Finally, the applicability of the biosensor is evaluated by measuring atropine sulfate in real samples with good accuracy.

Redox targeting of DNA anchored to MWCNTs and TiO2 nanoparticles dispersed in poly dialyldimethylammonium chloride and chitosan.

A key issue associated with electrochemical DNA-based biosensors is how to enhance DNA immobilization on the substrates. In order to improve the immobilization of DNA and to optimize DNA interaction efficiency, different kinds of strategies have been developed. In this regard, nanomaterials have attracted a great deal of attention in electrode surface modification for DNA biosensor fabrication. In this study, nanostructured films were deposited at the surface of a pencil graphite electrode (PGE) as a working electrode. For the present purpose, common polyelectrolytes are used for surface modification with double-stranded DNA. Two positively charged polyelectrolyte, namely poly dialyldimethylammonium chloride (PDDA) and chitosan, are initially compared for DNA immobilization at the surface of MWCNTs and TiO2 nanoparticles (TiO2NPs). In a second step, the basic electrochemical properties of the sensors are investigated using voltammetric methods. The modified electrodes are also characterized by scanning electron microscopy and electrochemical impedance measurements. It will be shown that electrode modification with DNA and the nanostructure that disperses in PDDA leads to an enhanced sensitivity of the DNA voltammetric detection mechanism. In a previous study, a comparison was done between MWCNTs and TiO2NPs for determining the effect of nanoparticle effect on DNA immobilization on the electrode surface. In order to compare the efficiency of the prepared DNA-based biosensors, methylene blue is chosen as an electroactive probe. It will be shown that the stability of the immobilized DNA within several days will be much higher when MWCNTs rather than TiO2NPs are used.

Improved immobilization of DNA to graphite surfaces, using amino acid modified clays.

Assessment of the interaction of small molecules with DNA, hybridization assays for DNA sequence analysis and diagnostics and the investigation of DNA damage involves the immobilization of an array of oligonucleotides onto a solid substrate. Herein, a new nano sized DNA-based biosensor containing valine (Val) amino acid organo-modified Cloisite Na+ as a new bionanohybrid film for the immobilization of DNA was developed. The Cloisite-Val organoclay was synthesized by a cation-exchange method, which involves the displacement of the sodium cations of Cloisite Na+ with the ammonium ions of the Val-amino acid. The synthesized materials were characterized with different methods such as FT-IR spectroscopy, TEM, SEM, XRD and electrochemical impedance spectroscopy (EIS). The nanostructured film was deposited at the surface of a working graphite electrode and utilized for the surface modification with double-stranded DNA. It was found that the electrode modification with DNA and Cloisite-Val leads to an enhanced sensitivity in the DNA voltammetric detection compared with other modified electrodes that were used for this work. The efficiency of DNA immobilization was followed by means of EIS and voltammetry. Immobilization is much more rapid when using the Cloisite-Val modified graphite support than when employing conventional supports. The stability of the immobilized DNA over several days has been found to be much higher when using the new support than in preparations using conventional ones.

DNA-based biosensor for comparative study of catalytic effect of transition metals on autoxidation of sulfite.

The transition metal-catalyzed oxidation of sulfur(IV) oxides has been known for more than 100 years. However, to the best of the authors' knowledge, no electrochemical quantitative study has yet been carried out to determine its nature. In view of the transition metal catalyzed oxidation of sulfur(IV) oxides, a series of radicals are involved in the overall reaction process whereby the sulfite, in the presence of transition metals, may cause damages to DNA through the generation of these highly reactive species. In the present work, {MWCNTs-PDDA/DNA}(2) layer-by-layer (LBL) films were prepared to detect DNA damage induced by radicals generated from sulfite autoxidation using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The change in the peak potential separation (ΔE(p)) and charge transfer resistance (R(p)) after incubation of the DNA biosensor in the damaging solution for a certain time was used as indicators of DNA damage. It was found that sulfite in the presence of Co(II), Cu(II), Cr(VI), Fe(III), and Mn(II) caused damage to DNA while neither sulfite alone nor metal ions alone did have the same effect. The results suggest that sulfite is rapidly autoxidized in the presence of Co(II), Cu(II), Cr(VI), Fe(III), and Mn(II), producing radicals that cause the DNA damage. These radicals can be ranked in a descending order of their ability to induce DNA damage with sulfite as follows: Fe(III) > Co(II) > Cu(II) > Cr(VI) > Mn(II). The DNA damage induced by sulfite plus Co(II), Cr(VI), and Fe(III) was inhibited by primary alcohols, but they were not when superoxide dismutase (SOD) and tert-butyl alcohol were used. Comparison of methods used to determine the minimum concentration of a transition metal for sulfite induced DNA damage revealed that electrochemical impedance spectroscopy and cyclic voltammetry outperformed the quantitative comparison of different reagents.

A novel sensitive DNA-biosensor for detection of a carcinogen, Sudan II, using electrochemically treated pencil graphite electrode by voltammetric methods.

A simple and inexpensive methodology was used to develop a novel electrochemical sensor for the determination of Sudan II. The interaction of Sudan II with salmon sperm ds-DNA on the surface of salmon sperm ds-DNA-modified pencil graphite electrode (PGE) and in solution phase was studied, using differential pulse voltammetry. The difference between adenine and guanine signals of the ds-DNA after and before interaction with Sudan II was directly proportional to Sudan II concentration, which used for quantitative inspections. Using PGE, a linear calibration curve (R(2)=0.9958) was observed with 0.5-6.0 µg mL(-1) Sudan II. Furthermore, the LOD of 0.4 µg mL(-1) and linear range between 0.5 and 4.0 µg mL(-1) were achieved in solution phase. In the second part, Sudan II was determined on a pretreated pencil graphite electrode by means of adsorptive stripping differential pulse voltammetry. The peak current was linearly dependent on Sudan II concentration over the range of 0.0015-0.30 µg mL(-1), with a detection limit of 0.00007 µg mL(-1) Sudan II. Both ds-DNA-modified PGE and PPGE were applied to analyze Sudan II in real samples.

DNA-functionalized biosensor for riboflavin based electrochemical interaction on pretreated pencil graphite electrode.

The interaction of riboflavin with salmon sperm double-stranded DNA based on the decreasing of the oxidation signal of guanine and adenine bases was studied electrochemically with a pencil graphite electrode (PGE) using differential pulse voltammetry. The decrease in the intensity of the guanine and adenine oxidation signals after interaction with riboflavin was used as an indicator signals for the sensitive determination of riboflavin. Under the optimum conditions, a linear dependence of the guanine and adenine oxidation signals was observed for the riboflavin concentration in the range of 0.5-70 µg mL(-1) with a detection limit of 0.34 µg mL(-1) at ds-DNA modified PGE. The reproducibility and applicability of the analysis to pharmaceutical dosage forms and urine sample were also investigated. These results showed that this DNA biosensor could be used for the sensitive, rapid, simple and cost effective detection and determination of riboflavin-ds-DNA interaction. Pretreated pencil graphite electrode (PPGE) was also used for the determination of riboflavin by differential pulse adsorptive stripping voltammetry. With PPGE, a linear relationship was obtained for riboflavin over the concentration range of 0.003-0.88 µg mL(-1) with differential pulse adsorptive stripping voltammetric signal and with a detection limit of 0.076 ng mL(-1). Both determination methods were fully validated and applied for the analysis of riboflavin.