Enhancing the degree of functional multiplexing while assuring operational reliability and manufacturability at competitive costs are crucial components to enable comprehensive sample-to-answer automation, e.g., for use in common, decentralized “Point-of-Care” or “Point-of-Use” scenarios. This paper demonstrates a model-based ‘digital twin’ approach which efficiently supports the algorithmic design optimization of exemplary centrifugo-pneumatic (CP) dissolvable-film (DF) siphon valves towards larger-scale integration (LSI) of well-established “Lab-on-a-Disc” (LoaD) systems. Obviously, the spatial footprint of the valves and their upstream laboratory unit operations (LUOs) have to fit, at a given radial position prescribed by its occurrence in the assay protocol, into the locally available disc space. At the same time, the retention rate of rotationally actuated valve and, most challenging, its band width related to unavoidable experimental tolerances need to slot into a defined interval of the practically allowed frequency envelope. A set of design rules, metrics, and methods and instructive showcases for computationally assisted optimization of valve structures are presented.