The evaluation of epigenetic features such as DNA methylation is becoming increasingly important in many biochemical processes like gene expression and transcription as well as in several diseases like schizophrenia or diabetes. Here, we report that self-assembled nanomechanical resonators entirely composed of DNA molecules can be used to explore gross changes in DNA methylation levels (0-25-50%), while careful control of tensile stress is needed to reduce the variability of resonance frequency for rigorous quantification. The effect of the tensile stress retained by the suspended DNA nanoresonators on the application of the technique is extensively explored using a combination of laser Doppler vibrometry and atomic force spectroscopy. DNA nanoresonators are real-time, label-free sensors and could avoid chemical functionalization and sample amplification. Therefore, they may represent in the future a key complementary routine tool for global DNA methylation analysis needed to evaluate the consequences of environmental stresses on the human genome.

Despite being widely recognized as of paramount importance in molecular biology, real-time monitoring of structural transitions in DNA complexes is currently limited to complex techniques and chemically modified oligonucleotides. Here, we show that nanomechanical resonators made of different DNA complexes, such as pristine dsDNA, ssDNA, and DNA intercalated with dye molecules or chemotherapeutic agents, are characterized by unique fingerprint curves when their flexural resonance frequency is tracked as a function of temperature. Such frequency shifts can be successfully used to monitor structural variations in DNA complexes, such as B-to-A form and helix-to-coil transitions, thus opening implications in both environmental studies-for example, trucking the effects of heavy metal exposure on human or vegetable DNA molecules-and in vitro experiments for the evaluation of the effects of drugs on patient DNA.

Reaching reproducible strong coupling between a quantum emitter and a plasmonic resonator at room temperature, while maintaining high emission yields, would make quantum information processing with light possible outside of cryogenic conditions. We theoretically propose to exploit the high local curvatures at the tips of plasmonic nanocubes to reach Purcell factors of >106 at visible frequencies, rendering single-molecule strong coupling more easily accessible than with the faceted spherical nanoparticles used in recent experimental demonstrations. In the case of gold nanocube dimers, we highlight a trade-off between coupling strength and emission yield that depends on the nanocube size. Electrodynamic simulations on silver nanostructures are performed using a realistic dielectric constant, as confirmed by scattering spectroscopy performed on single nanocubes. Dimers of silver nanocubes feature Purcell factors similar to those of gold while allowing emission yields of >60%, thus providing design rules for efficient strongly coupled hybrid nanostructures at room temperature.

The Raman spectra of DNA fibers were studied before and after suspension over superhydrophobic surface (SHS). At the end of the dehydration process of a droplet of nucleic acids solution over SHS, two structural areas appear: (i) a thicker droplet residual spot and (ii) a thinner free-standing, self-oriented DNA extended fibers region. For specimens deposited on reference samples (CaF2 slides), buffer contribution overrides the total Raman spectrum, while for free-standing lambda DNA, biological signature comes out readily with no interference. Our spectroscopy results confirm that a mechanical sieving effect occurs spontaneously during lambda DNA suspension process over superhydrophobic devices. Tailored designed devices and sample preparation separate small non-interacted molecules from the bundles and remove, concentrating, the non-suspended material in a defined area of the SHS. At the end of the process, helices retain only the ions that effectively have interacted with the DNA strand in solution, while all the other compounds were sieved away from the areas of interest. The self-sieving effect herein shown will provide a step forward for biomaterials studies as it allows the characterization of dilutions otherwise not detectable. The samples, autonomously purified, retain the effective interaction with environmental stresses free from any other misleading contribution allowing for characterization in optimal condition.

This review looks at the different approaches, techniques, and materials devoted to DNA studies. In the past few decades, DNA nanotechnology, micro-fabrication, imaging, and spectroscopies have been tailored and combined for a broad range of medical-oriented applications. The continuous advancements in miniaturization of the devices, as well as the continuous need to study biological material structures and interactions, down to single molecules, have increase the interdisciplinarity of emerging technologies. In the following paragraphs, we will focus on recent sensing approaches, with a particular effort attributed to cutting-edge techniques for structural and mechanical studies of nucleic acids.