Aptasensing Interfaces: Setting the Stage Right for Optimal Sensor Performance

Dear Colleagues,

It gives me great pleasure to announce this Special Issue, which is dedicated to aptasensors and the complex intra- and inter-moleculer forces acting on aptamers at solid–liquid interfaces. It is well known that surface confinement can have a large impact on a biomolecule’s conformation, which, in the case of biosensors, can in turn affect the sensitivity and/or selectivity of the detection of target analytes. Εven though the effect of these immobilization-induced phenomena on proteins has been extensively studied, the mechanisms behind aptamer adsorption or covalent attachment to a solid support and the influence of a surface’s physicochemical properties on the former’s 3D shape remain rather obscure. This is quite paradoxical, considering the sensitivity of aptamers to their surrounding environment and the considerable analytical performance enhancement that could be achieved if their optimal chemistry, linker, and spacer were employed in the fabrication of an aptasensor.

Therefore, the main goal of this Special Issue is to address the lack of or fragmented knowledge on aptasensing interfaces by beginning an experimental data-driven categorization of the different variables affecting an aptamer’s conformation and a systematic investigation into the interfacial forces governing its freedom to move, which collectively determine its ability to recognise analytes. To this end, investigations that take a holistic approach to the topic would be of tremendous benefit as they would ultimately allow for the formulation of definitive, generally applicable rules concerning surface-tethered aptamers and the generation of a toolbox of hints, tips, and warnings to guide and drive aptasensor development in the future.

It would be interesting, for example, to investigate if and how an aptamer’s conformation, be it stem-loop or G-quadruplex, structure-switching or not, dictates the choice of spacer or how the latter could be further optimized with respect to the detection of the same analyte by the same aptamer but in media of different polarities. Equally importantly, this Special Issue welcomes contributions that focus on smart techniques devised to characterize the behaviour of aptamers at solid–liquid interfaces, which in itself poses a major obstacle to our understanding of these molecules, and especially so in the context of aptamers against small molecules.

Lastly, the aim of this Special Issue is to extend beyond the elucidation of the fundentamental principles of aptasensing interfaces and to put this knowledge into practice. I hope, therefore, to see original and review publications where existing or newly acquired information on the structural rearrangements and/or alterations an aptamer inevitably undergoes upon surface confinement is exploited for the enhancement of selectivity/sensitivity, or to achieve a wider dynamic range of detection. Equally, this could even be taken into account right from the beginning, through the implementation of an ‘optimized by design’ principle in the aptamer’s selection and the development of an aptasensor.

It is my firm belief that taking a holistic approach to aptasensing interfaces, one that encompasses all possible parameters, including ones commonly overlooked, such as the influence of surface chemistry on the quantity and orientation of an immobilized aptamer, and attempting to gain an in-depth understanding of the intricate interplay between them is the only way for aptasensors to realize their full potential. I sincerely hope that this Special Issue and your contributions will become the starting point for a fruitful discussion that will complement the remarkable progress already accomplished in the field of aptamers, advance their implementation in biosensors, and set the tone for future investigations in the field.

Dr. George Tsekenis
Prof. Dr. Michael Thompson
Guest Editors

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• aptamer conformation
• aptamer immobilization
• aptamer-based sensors
• effect of spacers and linkers on aptamers
• surface chemistries of aptasensors
• interfacial characterization techniques