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As digital microfluidics-based biochips find more applications, their complexity is expected to increase significantly owing to the trend of multiple and concurrent assays on the chip. There is a pressing need to deliver a top-down design methodology that the biochip designer can leverage the same level of computer-aided design support as the semi-conductor industry now does. Moreover, as microelectronics fabrication technology is scaling up and integrated device performance is improving, it is expected that these microfluidic biochips will be integrated with microelectronic components in next-generation system-on-chip designs. This study presents the analysis and experiments of digital microfluidic operations on a novel electrowetting-on-dielectric-based `micro-electrode dot array architecture` that fosters a development path for hierarchical top-down design approach for digital microfluidics. The proposed architecture allows dynamic configurations and activations of identical basic microfluidic unit called `micro-electrode cells` to design microfluidic components, layouts, routing, microfluidic operations and applications of the biochip hierarchically. Fundamental microfluidic operations have been successfully performed by the architecture. In addition, this novel architecture demonstrates a number of advantages and flexibilities over the conventional digital microfluidics in performing advanced microfluidic operations.