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Towards the Development of Novel Supramolecular Receptor-based Plasmonic Nanosensors

par Fantoni, Alessia
Président du jury Bartik, Kristin
Promoteur Bruylants, Gilles ;Dalla Cort, Antonella
Publication Non publié, 2025-01-20

Thèse de doctorat

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Résumé :

The development of molecular sensors that function in aqueous environments and provide easily readable signals is crucial in advancing diagnostic technology. Traditional detection methods, such as chromatography and mass spectrometry, require sophisticated instrumentation, limiting their accessibility in practical applications. In response, there is a growing interest in developing more user-friendly, cost-effective sensors that can reliably detect target analytes without complex equipment or trained operators. This thesis focuses on the integration of supramolecular chemistry and nanoscience to design versatile, water-compatible plasmonic nanosensors. The primary goal was to explore how the host-guest properties of specific supramolecular receptors can be combined with the plasmonic characteristics of gold nanoparticles (AuNPs) to develop colorimetric sensors capable of detecting target molecules with high selectivity. These systems were evaluated for sensing applications both in solution and as part of paper-based lateral flow assays (LFAs). By employing small organic supramolecular receptors instead of traditional biomolecules, this study aimed to address the limitations of conventional LFAs, such as the high cost and instability of antibodies, thereby providing a more versatile and robust alternative for targeted detection.The research is divided into two main studies: one employing Zn(II)-salophen receptors for di-carboxylate species detection and the other utilizing a p-tert-butyl-calix[5]arene derivative for di-ammonium species detection, both integrated with AuNPs as colorimetric transducers.In the first study, new Zn(II)-salophen receptors were synthesized with functional groups allowing their efficient grafting onto AuNPs via different strategies: thiols for direct grafting (SalA) or a carboxylate (SalB, SalC) for coupling to ammoniums (post-functionalisation) present on PEG chains coating the AuNPs. One receptor was decorated with hydrophilic groups to enhance the colloidal stability of the functionalized particles (SalC). Binding studies in organic solvents showed strong affinity of the receptors for acetate via Lewis acid-base interactions, with SalC maintaining its effectiveness in water. These results underscore the potential of Zn(II)-salophen receptors for integration into AuNP-based nanosensors. The subsequent phase explored the functionalization of AuNPs with these Zn(II)-salophen derivatives to create effective plasmonic nanosensors for dicarboxylate detection. Various grafting strategies were investigated. Key factors such as the grafting strategy, the organic coating composition and density, and the receptor orientation were optimized to enhance stability and ensure effective interaction with target dicarboxylates. The sensing ability of these systems was then evaluated through aggregation-based mechanisms, where analyte binding induced AuNPs aggregation, leading to observable colour changes. Initial challenges in sensor performance were addressed by optimizing the receptor positioning through the post-functionalization process, leading to significantly enhanced stability and reliable aggregation behaviour, particularly with SalB-modified AuNPs.Building on these results, the research then shifted focus to developing paper-based lateral flow assays (LFAs). The known biotin/streptavidin complexation strategy was adapted to design a method for immobilizing SalB onto nitrocellulose membrane. While further optimizations are needed to enhance the performance of SalB-based assay, this method provides a foundational model for future paper-based assays utilizing organic receptors. In the second study, the research was expanded to a different class of receptors, focusing on the detection of diammonium species using a p-tert-butyl-calix[5]arene derivative (Calix[5]). By leveraging the known strong host-guest interactions and the selectivity of this receptor toward primary alkylammonium chains, we developed a novel sensor. This system demonstrated the remarkable ability to selectively recognize long diammonium chains, such as 1,12-dodecandiammonium, whose optimal length facilitates the intracavity encapsulation of the ammonium groups, leading to AuNP aggregation and a observable colour change. Transitioning this system to a dipstick format successfully enabled selective recognition of long diammonium chains in paper-based assays, marking the first example of diammonium detection using LFAs. This innovation presents significant potential for non-invasive diagnostics, particularly for detecting polyamine biomarkers in medical applications.In conclusion, this research not only expands the application of supramolecular receptors in nanosensing but also establishes a foundation for the innovative integration of organic receptors into paper-based diagnostic systems, paving the way for more accurate and accessible detection methods across various fields.