Portable and automated analyzer for rapid and high precision in vitro dissolution of drugs.

We developed a novel portable and automated dissolution test analyzer for rapid and high precision in vitro dissolution testing of drugs. The analyzer consists of a flow-through-cell drug dissolution system, an automated sequential sampling system, a high-speed capillary electrophoresis (HSCE) system, and a data acquisition system. Combining the high-temporal resolution flow-gating sampling approach with HSCE, which has outstanding advantages of efficient separation and resolution, the analyzer can achieve rapid analysis and exhibits the ability in miniaturization for on-site assessment of different active pharmaceutical ingredients. To integrate the flow-through-cell dissolution system with HSCE, a specially designed flow-gating-injection (FGI) interface was employed. The performance of the analyzer was investigated by analyzing the dissolution of immediate-release drugs including single dose (amoxicillin dispersible tablets) and fixed dose combination (amoxicillin and clavulanate potassium) drug tablets with the high-temporal resolutions of 12 s and 20 s, respectively. The dissolution profiles of different active pharmaceutical ingredients could be simultaneously and automatically monitored with high repeatability and accuracy. The analyzer was successfully utilized for the pharmaceutical quality control and bio-relevant dissolution testing, as well as in vivo-in vitro correlation analysis. Our portable analyzer is miniaturized, convenient and of low-cost, and will provide a valuable tool for dissolution testing in pharmaceutical research and development.

Capillary electrophoresis-integrated immobilized enzyme microreactor with graphene oxide as support: Immobilization of negatively charged L-lactate dehydrogenase via hydrophobic interactions.

We report the first application of hydrophobic interaction between graphene oxide (GO) and negatively charged enzymes to fabricate CE-integrated immobilized enzyme microreactors (IMERs) by a simple and reliable immobilization procedure based on layer by layer assembly. L-lactate dehydrogenase (L-LDH), which is negatively charged during the enzymatic reaction, is selected as the model enzyme. Various spectroscopic techniques, including SEM, FTIR, and UV-vis are used to characterize the fabricated CE-IMERs, demonstrating the successful immobilization of enzymes on the negatively charged GO layer in the capillary surface. The IMER exhibits excellent repeatability with RSDs of inter-day and batch-to-batch less than 3.49 and 6.37%, respectively, and the activity of immobilized enzymes remains about 90% after five-day usage. The measured Km values of pyruvate and NADH of the immobilized L-LDH are in good agreement with those obtained by free enzymes. The results demonstrate that the hydrophobic interactions and/or π-π stacking is significant between the GO backbone and the aromatic residues of L-LDH and favorable to fabrication of CE-integrated IMERs. Finally, the method is successfully applied to the determination of pyruvate in beer samples.

Enzyme-like catalysis of polyoxometalates for chemiluminescence: Application in ultrasensitive detection of H2O2 and blood glucose.

We show that vanadomolybdophosphoric heteropoly acid (H5PMo10V2O40, PMoV2), one of the polyoxometalates (POMs), presents peroxidase-like activity that can catalyze the luminol/H2O2 reaction to generate chemiluminescence (CL) emission. Based on this foundation, we report an enzyme-free luminol/H2O2/PMoV2 CL system that can be utilized for the ultrasensitive detection of H2O2. The CL intensity exhibits good linear dependence on H2O2 concentration in a wide range up to 5000 nM with a limit-of-detection of 5 nM. The method was successfully used for the determination of glucose in human serum. Our study paves the way for the application of functional POM materials in a variety of biosensing assays, such as the determination of cholesterol, uric acid, lactate, etc., in which H2O2 is a product of oxidoreductase enzymes.

Synthesis of TiO2-polyaniline core-shell nanofibers and their unique UV photoresponse based on different photoconductive mechanisms in oxygen and non-oxygen environments.

The TiO2-polyaniline (PANI) core-shell nanofibers with unique ultraviolet (UV) photoresponse were designed and fabricated. When the core-shell nanofibers were tested in an oxygen (O2) and a non-oxygen environment under UV illumination, respectively, a decrease and an increase in photoconduction were observed, which suggested different photoconductive mechanisms of the core-shell materials in different environments.

Electrochemical biosensors based on redox carbon nanotubes prepared by noncovalent functionalization with 1,10-phenanthroline-5,6-dione.

To improve the electrocatalytic activities of carbon nanotubes (CNT) towards the oxidation of nicotinamide adenine dinucleotide (NADH), we derive them with a redox mediator, 1,10-phenanthroline-5,6-dione (PD), by the noncovalent functionalization method. The redox carbon nanotubes (PD/CNT/GC) show excellent electrocatalytic activities towards the oxidation of NADH (catalytic reaction rate constant, k(h) = 7.26 × 10(3) M(-1) s(-1)), so the determination of NADH can be achieved with a high sensitivity of 8.77 µA mM(-1) under the potential of 0.0 V with minimal interference. We also develop an amperometric ethanol biosensor by integration of alcohol dehydrogenase (ADH) within the redox carbon nanotubes (PD/CNT/GC). The ethanol biosensor exhibits a wide linear range up to 7 mM with a lower detection limit of 0.30 mM as well as a high sensitivity of 10.85 nA mM(-1).

Electrochemical sensors based on binuclear cobalt phthalocyanine/surfactant/ordered mesoporous carbon composite electrode.

A new ordered mesoporous carbon (OMC) composite modified electrode was fabricated for the first time. Binuclear cobalt phthalocyaninehexasulfonate sodium salt (bi-CoPc) can be adsorbed onto didodecyldimethylammonium bromide (DDAB)/OMC film by ion exchange. UV-vis spectroscopy, scanning electron microscopy (SEM) and electrochemical methods were used to characterize the composite film. The cyclic voltammograms demonstrate that the charge transfer of bi-CoPc is promoted by the presence of OMC. Further study indicated that bi-CoPc/DDAB/OMC film is the excellent electrocatalyst for the electrochemical reduction of oxygen in a neutral aqueous solution and hemoglobin (Hb) at lower concentrations. Additionally, as an amperometric 2-mercaptoethanol (2-ME) sensor, this modified electrode shows a wider linear range (2.5 x 10(-6) to 1.4 x 10(-4) M), high sensitivity (16.5 microA mM(-1)) and low detection limit of 0.6 microM (S/N=3). All these confirm the fact that the new composite film may have wide potential applications in biofuel cells, biological and environmental sensors.

Identification of rhubarbs by using NIR spectrometry and temperature-constrained cascade correlation networks.

Temperature-constrained cascade correlation networks (TCCCNs) were used to identify powdered rhubarbs based on their near-infrared spectra. Different network configurations that used multiple network models with single output (Uni-TCCCN) and single networks with multiple outputs (Multi-TCCCN) were compared. Comparative studies were made by using Latin-partitions and leave-one-out cross-validation methods. Results showed that multiple networks with single output predicted generally better than single network with multiple outputs. Better results with TCCCN models were obtained compared with conventional back propagation neural networks (BPNNs). The effects of parameters on correct identification and parameter optimizations were discussed in detail. With optimized neural network training parameters, NIR spectra from powdered rhubarb samples were classified by a TCCCN model with 100% accuracy.

The control of phthalocyanine properties through nitro-group electronic effect.

The UV-vis spectra of peripherally substituted tetranitrometallophthalocyanines (TNMPcs) 1a-1d and non-peripherally substituted TNMPcs 2a-2d were investigated. In comparison of 1a with 2a, there is the only difference in the substitution position of nitro-groups. The structural diversity of 1a and 2a resulted in different electronic effects of nitro-group on Pc rings, which caused them have two kinds of Q bands. The Q band in the UV-vis spectra of 1a-1d was split into two peaks, which were obviously influenced by temperature, while no split was observed in the Q band of 2a-2d. We can draw a conclusion that tuning nitro-group electronic effect is an important approach for controlling the properties of Pcs.

Quality control of the powder pharmaceutical samples of sulfaguanidine by using NIR reflectance spectrometry and temperature-constrained cascade correlation networks.

Temperature-constrained cascade correlation networks (TCCCNs) were applied to the identification of the powder pharmaceutical samples of sulfaguanidine based on near infrared (NIR) diffuse reflectance spectra and their first derivative spectra. This work focused on the comparison of performances of the uni-output TCCCN (Uni-TCCCN) and multi-output (Multi-TCCCN) by near infrared diffuse reflectance spectra and their first derivative spectra of sulfaguanidine. The TCCCN models were verified with independent prediction samples by using the "cross-validation" method. The networks were used to discriminate qualified, un-qualified and counterfeit sulfaguanidines pharmaceutical powders. The results showed that single outputs network generally worked better than the multiple outputs networks, and the first derivative spectra were more suitable for the identification comparing with original diffuse reflectance spectra. With proper network parameters the pharmaceutical powders can be classified at rate of 100% in this work. Also, the effects of parameters and related problems were discussed.

[Library search of UV spectra of organic environmental pollutants by temperature-constrained cascade-correlation networks].

A temperature-constrained cascade-correlation network (TCCCN) was used to identify ultraviolet (UV) spectra of organic environmental pollutants. Library search for UV spectra is more difficult than that for infrared (IR) spectra, because the UV spectra overlap more severely than IR spectra. Besides, drift and noise in the measurement will have significant effect on UV library spectra search. Therefore, neural networks with fuzzy output should be a better alternative for the library search. The TCCCN is different from the commonly used BP networks in architecture. The processing units in the TCCCN are connected in a cascade mode, and a temperature constraint is introduced. Therefore, the TCCCN can reduce overtraining and fast training speed. TCCCN was used for library search of UV spectra in the present work and the effects of network parameters and noise were investigated. Results showed that better results were obtained with the TCCCN than with conventional correlation method.