Researchers in Germany have once again made a major breakthrough in bionanotechnology, this time in the area of solid-state nanopore sensors, enhancing their capabilities by fitting them with cover plates made of deoxyribonucleic acid (DNA). This major advance was made in part thanks to the DNA ORIGAMI DEVICES ('Single-molecule studies of protein-protein-DNA interactions, enabled by DNA origami') project, which has clinched a European Research Council (ERC) grant worth EUR 1.5 million under the EU's Seventh Framework Programme (FP7). This project has opened up novel opportunities for a systematic study of macromolecular interactions in biology and is likely to deepen our understanding of regulatory processes in biology. The findings of this latest study were presented in the journal Angewandte Chemie International Edition.
Anything in the nanoscale refers to something so small that it can only be measured in the billionth. In this case nanopores are very small holes, usually in synthetic materials like grapheme or silicone, and are used to analyse and sequence single nucleic acid molecules. Nanopore biotechnology offers one of the most promising approaches to single molecule detection and analysis.
What the researchers at the Technische Universitaet Muenchen (TUM) in Germany have achieved is enhancing the ability of solid-state nanopores by fitting them with cover plates made of DNA. These nanoscale cover plates, which have had central apertures tailored to various "gatekeeper" functions, are formed by so-called DNA origami. This is the art of making structures from DNA to fold into custom-designed structures with specified chemical properties. This represents a major breakthrough for the industry as a whole with far-reaching effects.
This achievement did not come easy and is the result of hard work by different teams over recent years. One team led by TUM’s Professor Hendrik Dietz focused its efforts on refining control over DNA origami techniques and demonstrating how structures made in this manner can enable scientific investigations in diverse fields. Another research team at TUM, led by Dr Ulrich Rant, was doing the same but in the field of solid-state nanopore sensors, where the basic working principle is to urge biomolecules of interest, one at a time, through a nanometre-scale hole in a thin slab of semiconductor material. When biomolecules pass through or linger in such a sensor, minute changes in electrical current flowing through the nanopore translate into information about their identity and physical properties.
By working together they were able to develop a new device concept which up till now had been purely hypothetical; this involved the placement of a DNA origami nanoplate over the narrow end of a conically tapered solid-state nanopore. By adjusting or "tuning" the size of the central aperture in the DNA nanoplate, they could filter the type of molecules that pass through according to size. Furthermore, by placing a single-stranded DNA receptor in the aperture as bait, they should enable sequence-specific detection of "prey" molecules. In principle, such a device could even serve as the basis of a novel DNA sequencing system.
'We're especially excited about the selective potential of the bait/prey approach to single-molecule sensing,' said Professor Dietz, 'because many different chemical components beyond DNA could be attached to the appropriate site on a DNA nanoplate.'
High-resolution sensing applications, such as DNA sequencing, will face some additional hurdles, however, as Dr Rant explained: 'By design, the nanopores and their DNA origami gatekeepers allow small ions to pass through. For some conceivable applications, that becomes an unwanted leakage current that would have to be reduced, along with the magnitude of current fluctuations.'