Supercritical CO2–Driven Designof Beryllium Molecularly Imprinted Polymers for Thermal Biosensors

Supercritical carbon dioxide (scCO2) offers a sustainable medium for molecularly imprinted polymer (MIP) synthesis, yet rational monomer selection under supercritical conditions remains largely unexplored. Here, molecular dynamics (MD) simulations were used as a pre–polymerization screening tool to investigate template–monomer interactions for L–leucine (LEU) imprinting in scCO2. A CO2 force field was adapted for relevant temperature and pressure conditions, and relative binding free energies together with cluster population analysis were used to compare candidate systems. A beryllium–curcumin complex (BeCU) combined with 2–vinylpyridine was identified as a favorable system at 60 °C and 300 bar. Guided by these computational trends, BeCU–based MIPs were synthesized in scCO2 and experimentally evaluated. The optimized LEU/BeCU (1:1) system exhibited an imprinting factor of 11.6 in static binding assays. The materials were subsequently integrated into heat–transfer method (HTM) thermal sensors using two different surface–functionalization strategies: particle immobilization and direct scCO2–assisted grafting onto plasma–activated aluminum substrates. Both sensing platforms enabled selective thermal detection of LEU over L–isoleucine in the 0.23–0.92 mM range, with limits of detection of 0.03 mM for the particle immobilization method and 0.06 mM for the direct scCO2–assisted grafting method. This work demonstrates that MD–assisted screening can guide scCO2–based MIP synthesis and supports metal–coordinated imprinting as a viable strategy for thermal biosensing platforms and promotes a scalable and sustainable solution for selective amino acid detection.