Significant progress in the development of miniaturized microfluidic systems has occurred since their inception over a decade ago. This is primarily due to the numerous advantages of microchip analysis, including the ability to analyze minute samples, speed of analysis, reduced cost and waste, and portability. This review focuses on recent developments in integrating electrochemical (EC) detection with microchip capillary electrophoresis (CE). These detection modes include amperometry, conductimetry, and potentiometry. EC detection is ideal for use with microchip CE systems because it can be easily miniaturized with no diminution in analytical performance. Advances in microchip format, electrode material and design, decoupling of the detector from the separation field, and integration of sample preparation, separation, and detection on-chip are discussed. Microchip CEEC applications for enzyme/immunoassays, clinical and environmental assays, as well as the detection of neurotransmitters are also described.

A new approach for the integration of dual contactless conductivity and amperometric detection with an electrophoresis microchip system is presented. The PDMS layer with the embedded channels was reversibly sealed to a thin glass substrate (400 microm), on top of which a palladium electrode had been previously fabricated enabling end-channel amperometric detection. The thin glass substrate served also as a physical wall between the separation channel and the sensing copper electrodes for contactless conductivity detection. The latter were not integrated in the microfluidic device, but fabricated on an independent plastic substrate allowing a simpler and more cost-effective fabrication of the chip. PDMS/glass chips with merely contactless conductivity detection were first characterized in terms of sensitivity, efficiency and reproducibility. The separation efficiency of this system was found to be similar or slightly superior to other systems reported in the literature. The simultaneous determination of ionic and electroactive species was illustrated by the separation of peroxynitrite degradation products, i.e. NO(3)(-) (non-electroactive) and NO(2)(-) (electroactive), using hybrid PDMS/glass chips with dual contactless conductivity and amperometric detection. While both ions were detected by contactless conductivity detection with good efficiency, NO(2)(-) was also simultaneously detected amperometrically with a significant enhancement in sensitivity compared to contactless conductivity detection.

Peroxynitrite (ONOO -) is a highly reactive species implicated in the pathology of several cardiovascular and neurodegenerative diseases. It is generated in vivo by the diffusion-limited reaction of nitric oxide (NO • ) and superoxide anion ( • O 2 -) and is known to be produced during periods of inflammation. Detection of ONOOis made difficult by its short half-life under physiological conditions (∼1 s). Here we report a method for the separation and detection of ONOOfrom other electroactive species utilizing a microchip electrophoresis device incorporating an amperometric detection scheme. Microchip electrophoresis permits shorter separation times (∼25 s for ONOO -) and higher temporal resolution than conventional capillary electrophoresis (several minutes). This faster analysis allows ONOOto be detected before substantial degradation occurs, and the increased temporal resolution permits more accurate tracking of dynamic changes in chemical systems.Oxidative stress and nitration are thought to be involved in the pathology of several cardiovascular diseases including stroke, myocardial infarction, hypertension, atherosclerosis, and chronic heart failure, as well as the neurodegenerative diseases multiple sclerosis, Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, and Huntington's disease. 1 Peroxynitrite (ONOO -) is a highly reactive, oxidizing species formed in vivo from the reaction of nitric oxide (NO • ) with the superoxide anion. The reaction between these two species occurs at a diffusion-limited rate (6 × 10 9 M -1 s -1 ) 2 that can supersede the scavenging of superoxide by superoxide dismutase (2 × 10 9 M -1 s -1 ). 1 In situations such as the proinflammatory state, peroxynitrite can be produced faster than it can be scavenged, resulting in oxidative insult.

Amorphous solid dispersions of clotrimazole in the polymer Kollidon VA64 were prepared as films in concentrations from 0% to 100% in 10% by weight increments. Nanoindentation was performed on each film at 18% and 49% relative humidity to assess the effect of drug loading and humidity on the mechanical properties of the solid dispersions. Although the addition of clotrimazole to the polymer reduces the glass transition temperature of the system as measured by differential scanning calorimetry, the hardness, reduced elastic modulus, and storage modulus were found to increase to values greater than those of either pure component up to drug loadings of approximately 60% by weight. Further addition of clotrimazole to the system resulted in decreased hardness and moduli with increased drug load. Dynamic vapor sorption of the dispersions shows that the hygroscopicity of the system is reduced as clotrimazole is added to the polymer.

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