RECEIVED DATE (to be automatically inserted after your manuscript is accepted if requiredaccording to the journal that you are submitting your paper to) CORRESPONDING AUTHOR FOOTNOTE. F. Javier del Campo. Tel.: +34-935.947.700; Fax number: +34-935.801.496. 2ABSTRACT. The diffusion domain approach is a general framework for the understanding, interpretation and prediction of the response of microelectrode arrays. This work exposes some of its limitations, particularly when dealing with nanoelectrode arrays of a few microns in size. This article provides an overview of the principles and assumptions underpinning the diffusion domain approach, and then applies it to the study of nanoelectrode arrays. The apparent disagreement between theory and experimental data, due to the importance of radial diffusion to nanoelectrode arrays compared to microelectrode arrays, is explained using simulations and experiments. The principle that an array of micro-or nano-electrodes eventually behaves as if the entire array were a single electrode of the size of the array, with its corresponding properties, applies always. However, while microelectrode arrays tend to behave as macroelectrodes, nanoelectrode arrays on the other hand may behave as microelectrodes.For the case of arrays of small numbers of electrodes, or array sizes of microns or less in size, this compromises one of the key assumptions of the diffusion domain approach, namely that inner electrodes in an array are equivalent, which may lead the unaware to erroneous conclusions.

An external electric field driven in-channel detection technique for on-chip electrochemical detection in micro fabricated devices is described based on a microfluidic system containing an array of 20 microband electrodes. It is shown that an external electric field induces a potential difference between two gold microband electrodes in a poly(dimethylsiloxane) (PDMS) microchannel, and that this enables the electrochemical detection of electroactive species such as ascorbic acid and Fe(CN) 6 (4-). The results, which are supported by simulations of the behavior of the microband electrodes in the microfluidic system, show that the induced potential difference between the electrodes can be controlled by altering the external electric field or by using different microbands in the microband array. As the obtained currents depend on the concentrations of electroactive species in the flowing solution and the detection can be carried out anywhere within the channel without interference of the external electric field, the present approach significantly facilitates electrochemical detection in capillary electrophoresis. This approach consequently holds great promise for application in inexpensive portable chip-based capillary electrophoresis (CE) devices.