Programmable and sustainable scaling up of squaramide-based compounds through customizable paper-based platforms

The transition toward sustainable chemical manufacturing requires reaction systems that are scalable, energy-efficient, and inherently aligned with Green Chemistry principles. Here, we introduce the first programmable strategy for paper-based scale-up organic synthesis, revisiting the use of filter paper as predictive manufacturing platform, rather than a mere analytical substrate and an innovative support for chemical reactions. By utilizing wax-patterned paper-based platforms with tunable diameters, we establish quantitative relationships between platform's geometry, reagent loading, and product yield, enabling seamless translation from microliter screening to multi-gram synthesis. Using squaramide synthesis as a model, we demonstrate that increasing paper-based platform's size preserves reaction efficiency while maintaining outstanding green metrics, including a constant E-factor, high atom and carbon efficiencies, and excellent EcoScale scores. To further enable preparative-scale operation, large paper-based platforms are integrated into a modular 3D-printed scaffold that enhances mechanical stability and suppresses solvent evaporation. Unlike conventional scale-up strategies requiring complex flow equipment or energy-intensive infrastructure, our pump-free, cost effective and highly accessible platform exploits paper's porosity and capillary-driven transport to achieve on-demand, sustainable manufacturing. This work establishes paper as a new programmable reaction platform, offering a scalable, low-cost, and customizable solution toward decentralized and environmentally responsible chemical synthesis.