Self-regulating and autonomous microfluidic devices are essential for the long-term development of versatile biological and chemical platforms, including point-of-care molecular diagnostics and on-site chemical assays. However, regulating microfluidic systems without substantial manufacturing complexity has proven to be a considerable challenge. Previously, researchers have utilized valve components that are directly pressure actuated. These systems can be modified to enable pressure gain (i.e., using low-pressure control channels to actuate valves in high-pressure flow channels), but have generally required at least four microfluidic layers. Thus, we introduce a single-layer microfluidic device - built from guided microstructures constructed in situ via optofluidic lithography - with differential area ratios (R) that enable a static gain much greater than unity. Non-unity gain allows moving pistons to close against a higher pressure, and could be used as a dynamic microfluidic control mechanism. COMSOL simulations suggest pressure gains approaching R. Experimental results revealed pressure gain between 6.30±0.23 (for R = 10) and 1.94±0.09 (for R = 2).