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A direct and soft synthesis of biomimetic imprints in a stationary phase via sol-gel polymerization of silylated amino acids for selective separation of proteins
 

A direct and soft synthesis of biomimetic imprints in a stationary phase via sol-gel polymerization of silylated amino acids for selective separation of proteins

Yoann Ladner, Margaux Clavié, Jérémie Gouyon, Tristan Corbalan, Raquel Gutiérrez-Climente, Giang Ngo, Pascal Etienne, Philippe Rondard, Pierre-André Lafon, Pascal Dumy, …
Analytica Chimica Acta, Vol.1419
10/2026
Biomimetic imprinting, Molecular recognition, Silylated amino acid, Protein separation, Capillary electrochromatography
Molecularly imprinted polymers (MIPs) are promising artificial receptors for biomolecular recognition, yet protein imprinting remains challenging due to denaturation and mass-transfer limitations during polymerization. Here, we report a soft and straightforward strategy to create biomimetic imprints directly inside silica capillaries via sol–gel polymerization of silylated amino acids under biocompatible conditions. The approach relies on the polymerization of silylated amino acids around adsorbed protein templates, generating hybrid organic–inorganic cavities that combine shape complementarity with tailored chemical functionalities. The resulting open-tubular imprinted capillaries were evaluated by capillary electrochromatography using proteins of different size and isoelectric point. All imprinted materials exhibited strong and selective recognition of their target proteins, with selective retention ratios exceeding 5, whereas non-target proteins displayed values below 2. The coatings showed excellent repeatability and long-term stability, with variations below 5% in electrochromatographic performance. Selective separations were achieved for several protein templates including lysozyme, ribonuclease A, cytochrome C, α-lactalbumin and bovine serum albumin. Importantly, the imprinted capillaries maintained their selectivity in human plasma samples. The strategy was further extended to a nanobody template, yielding selective antibody-like molecular recognition in a complex biological matrix. This work demonstrates a versatile and protein-compatible route to create biomimetic recognition sites directly within capillary stationary phases. The proposed platform offers new opportunities for selective bioseparation, biomolecular analysis, and affinity-based analytical technologies.

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https://doi.org/10.1016/j.aca.2026.345872
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