Continuous-flow microfluidic biochips (CFMBs) are widely used in biochemical analysis due to their high precision and reliability. CFMBs consist of a flow layer and a control layer. To manage complex logic in the control layer with limited control pins, multiplexers are widely adopted. However, the physical design of multiplexers—specifically the co-optimization of valve placement and channel routing—remains largely unexplored. To address this, this paper proposes a co-optimization method based on Discrete Particle Swarm Optimization (DPSO). First, valve placement regions are constrained via preprocessing to ensure routing feasibility. Second, a DPSO framework encodes placement into particle positions and utilizes an embedded A* router to provide routing cost as fitness, establishing a closed-loop feedback mechanism between placement and routing. Third, X-architecture routing is introduced to expand the solution space and minimize wirelength. Experimental results demonstrate that the proposed method reduces the average control channel length by 8.27%. Notably, the X-architecture contributes a 5.01% improvement over traditional R-type routing, significantly enhancing both layout quality and routing efficiency.