Programmable and sustainable scaling up of squaramide-based compounds through customizable paper-based platforms.
4 affiliations
- 1Department of Pharmacy (DoE 2023-2027), University of Naples Federico II Via D. Montesano 49 Naples 80131 Italy [email protected] [email protected].
- 2Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University Philadelphia Pennsylvania 19122 USA.
- 3Bioelectronics Task Force at University of Naples Federico II Naples 80126 Italy.
- 4Department of Chemistry, Faculty of Science, Chulalongkorn University Bangkok 10330 Thailand.
Abstract
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.
Related
- Nucleic Acid Therapeutics in Rare Disease: From Precision Medicine to Programmable Platforms.
- Customizable Approach to Conformer Space Discretization using Torsion Angular Bin Strings (customTABS)
- PlasmiDB: an open-source and customizable database for plasmid lifecycle management in multi-user, multi-project plant molecular biology laboratories
- Benchmarking cell segmentation in two Spatialomics platforms with open-source software
- Beyond correlation: Intraclass correlation and bland-altman analysis reveal poor absolute agreement across multiplex cytokine immunoassay platforms
BibTeX
@article{kalligosfyri2026programmable,
title = {{Programmable and sustainable scaling up of squaramide-based compounds through customizable paper-based platforms.}},
author = {Panagiota M Kalligosfyri and Antonella Ilenia Alfano and Stefano Cinti and Margherita Brindisi},
journal = {RSC advances},
year = {2026},
month = oct,
doi = {10.1039/d6ra09121k},
url = {https://europepmc.org/article/MED/42903354},
note = {CC BY},
}
RIS
TY - JOUR
TI - Programmable and sustainable scaling up of squaramide-based compounds through customizable paper-based platforms.
AU - Panagiota M Kalligosfyri
AU - Antonella Ilenia Alfano
AU - Stefano Cinti
AU - Margherita Brindisi
PY - 2026
DA - 2026/10/20
JO - RSC advances
DO - 10.1039/d6ra09121k
UR - https://europepmc.org/article/MED/42903354
AB - 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.
SN - 2046-2069
ER -