Aptamers have emerged as promising biorecognition elements in the development of biosensors. The present work focuses on the application of quartz crystal microbalance with dissipation monitoring (QCM-D) for the enantioselective detection of a low molecular weight target molecule (less than 200 Da) by aptamer-based sensors. While QCM-D is a powerful technique for label-free, real-time characterization and quantification of molecular interactions at interfaces, the detection of small molecules interacting with immobilized receptors still remains a challenge. In the present study, we take advantage of the aptamer conformational changes upon the target binding that induces displacement of water acoustically coupled to the sensing layer. As a consequence, this phenomenon leads to a significant enhancement of the detection signal. The methodology is exemplified with the enantioselective recognition of a low molecular weight model compound, L-tyrosinamide (L-Tym). QCM-D monitoring of L-Tym interaction with the aptamer monolayer leads to an appreciable signal that can be further exploited for analytical purposes or thermodynamics studies. Furthermore, in situ combination of QCM-D with spectroscopic ellipsometry unambiguously demonstrates that the conformational change induces a nanometric decrease of the aptamer monolayer thickness. Since QCM-D is sensitive to the whole mass of the sensing layer including water that is acoustically coupled, a decrease in thickness of the highly hydrated aptamer layer induces a sizable release of water that can be easily detected by QCM-D.

The design and characterization of new ruthenium(II) complexes aimed at targeting G‐quadruplex DNA is reported. Importantly, these complexes are based on oxidizing 1,4,5,8‐tetraazaphenanthrene (TAP) ancillary ligands known to favour photo‐induced electron transfer (PET) with DNA. The photochemistry of complexes 1–4 has been studied by classical methods, which revealed two of them to be capable of photo‐abstracting an electron from guanine. From studies of the interactions with DNA through luminescence, circular dichroism, bio‐layer interferometry, and surface plasmon resonance experiments, we have demonstrated the selectivity of these complexes for telomeric G‐quadruplex DNA over duplex DNA. Preliminary biological studies of these complexes have been performed: two of them showed remarkable photo‐cytotoxicity towards telomerase‐negative U2OS osteosarcoma cells, whereas very low mortality was observed in the dark at the same photo‐drug concentration.

Surface plasmon resonance is a powerful technique for label-free and real-time characterization of molecular interactions at interfaces. However, the detection of small molecules still remains a challenge. Here, we report on the direct detection of a low molecular weight compound by its receptor presented as a monolayer. Moreover, the signal observed is more than twice the expected mass-weighted response. To establish the origin of the signal enhancement, we present herein a theoretical model that simulates the maximal SPR response by taking into account the aptamer conformational change. We demonstrated that the thickness layer variation is not the only parameter to be considered. We highlighted that the conformational transition of the aptamer also induces a deviation of the refractive index increment (RII) of the target /aptamer complex from the sum of the RII of individual entities. This non-additivity of the RII significantly contributes to the magnitude of the signal. We also propose the prediction of the maximal SPR response in function of the penetration depth, the ratio of the mass-weighted RII of the partners, the sensing layer thickness and the correction of the complex RII. This model provides new insights in parameters to be considered for analysis of SPR signals.

Aptamers have emerged as promising biorecognition elements for the development of biosensors. The present work focused on the direct detection, by surface plasmon resonance (SPR) and quartz crystal microbalance with dissipation monitoring (QCM-D), of a low molecular weight (LMW) compound (less than 200 Da) with an aptamer receptor presented as an oriented monolayer on surface. These techniques are powerful for label-free, real-time characterization and quantification of molecular interactions at interfaces. Herein, we analyzed the influence of aptamer surface density on the recognition properties. A decrease of the surface 2 concentration was shown to improve the affinity for the target due to a higher kinetic association constant that could be explained by a limitation of the steric hindrance of the aptamer on the surface. An aptamer folding is produced upon recognition of the LMW target that gives rise to the modification of the layer on the surface. This induces a displacement of water acoustically coupled to the sensing layer, a thickness layer variation and a deviation of the refractive index increment (RII) of the target/aptamer complex from the sum of the RII of individual entities. We also demonstrated that the recognition signal was still detectable for low aptamer density (lower than 1 pmol.cm-2).

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Telomeric regions containing G-quadruplex (G4) structures play a pivotal role in the development of cancers. The development of specific binders for G4s is thus of great interest in order to gain a deeper understanding of the role of these structures, and to ultimately develop new anticancer drug candidates. For several years, Ru complexes have been studied as efficient probes for DNA. Interest in these complexes stems mainly from the tunability of their structures and properties, and the possibility of using light excitation as a tool to probe their environment or to selectively trigger their reaction with a biological target. Herein, we report on the synthesis and thorough study of new Ru complexes based on a novel dipyrazino[2,3-a:2',3'-h]phenazine ligand (dph), obtained through a Chichibabin-like reaction. Luminescence experiments, surface plasmon resonance (SPR), and computational studies have demonstrated that these complexes behave as selective probes for G-quadruplex structures.

Robotic microhandling is a promising way to assemble microcomponents in order to manufacture a new generation of hybrid microelectromechanical systems. However, at the scale of several micrometers, the adhesion phenomenon highly perturbs the micro-object release and positioning. This phenomenon is directly linked to both the object and the gripper surface chemical composition. We propose to control the adhesion by using a chemical self-assembled monolayer on both surfaces. Different types of chemical functionalization have been tested, and this paper focuses on the presentation of aminosilane-grafted 3-(ethoxydimethylsilyl)propylamine and (3-aminopropyl)triethoxysilane. We show that the liquid pH can be used to modify the adhesion and to switch from an attractive behavior to a repulsive behavior. The pH control can thus be used to increase the adhesion during handling and cancel the adhesion during release. Experiments have shown that the pH control is able to control the release of a micro-object. This paper shows the relevance of a new type of reliable submerged robotic microhandling principle, which is based on adjustment of the chemical properties of the liquid.

Surface plasmon resonance (SPR) is a powerful technique for studying biomolecular interactions mainly due to its sensitivity and real-time and label free advantages. While SPR signals are usually positive, only a few studies have reported sensorgrams with negative signals. The aim of the present work is to investigate and to explain the observation of negative SPR signals with the hypothesis that it reflects major changes in ligand conformation resulting from target binding. We demonstrated that these negative unconventional signals were due to the negative complex (ligand/analyte) refractive index increment (RII) deviation from the sum of the RII of the individual entities which counterbalanced the theoretical increase of the signal triggered by the target recognition and the ligand folding. We also found that the conformation change of biomolecules can induce a negative or a positive complex RII deviation depending on its sequence and immobilization mode.