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The architecture and design of a compact, multichannel, hybrid-multiplexed potentiostat for performing electrochemical measurements on continuously-biased electrode arrays is presented. The proposed architecture utilises a combination of sequential and parallel measurements, to enable high performance whilst keeping the system low-cost and compact. The accuracy of the signal readout is maintained by following a special multiplexing approach, which ensures the continuous biasing of all the working electrodes of an array. After sampling the results, a digital calibration technique factors out errors from component inaccuracies. A prototype printed circuit board (PCB) was designed and built using off-the-shelf components for the real-time measurement of the amperometric signal of 48 electrodes. The operation and performance of the PCB was evaluated and characterised through a wide range of testing conditions, where it exhibited high linearity (R(2)>0.999) and a resolution of 400pA. The effectiveness of the proposed multiplexing scheme is demonstrated through electrochemical tests using KCl and [Fe(CN)6](3-) in KCl solutions. The applicability of the prototype multichannel potentiostat is also demonstrated using real biosensors, which were applied to the detection of IgA antibodies., (Copyright © 2013 Elsevier B.V. All rights reserved.)