Scaffolded biosensors with designed DNA nanostructures

In addition to its fundamental function as a genetic code carrier, the utilization of DNA in various material applications has been actively explored over the past several decades. DNA is intrinsically an excellent type of self-assembly nanomaterial owing to its predictable base-pairing, high chemical stability and the convenience it possesses for synthesis and modification. Because of these unparalleled properties, DNA is widely used as excellent recognition elements in biosensors and as unique building blocks in nanodevices. A critical challenge in surface-based DNA biosensors lies in the reduced accessibility of target molecules to the DNA probes arranged on heterogeneous surfaces, especially when compared to probe–target recognition in homogeneous solutions. To improve the recognition abilities of these heterogeneous surface-confined DNA probes, much effort has been devoted to controlling the surface chemistry, conformation and packing density of the probe molecules, as well as the size and geometry of the surface. In this review, we aim to summarize the recent progress on the improvement of the probe–target recognition properties by introducing DNA nanostructure scaffolds. A range of new strategies have proven to provide a significantly enhanced range in the spatial positioning and the accessibility of the probes to the surface over previously reported linear structures. We will also describe the applications of DNA nanostructure scaffold-based biosensors. The detection of nucleic acid – DNA and RNA – is crucial in various fields from life sciences research to clinical diagnosis and anti-bioterrorism. Beside its role as a carrier of genetic information, over the past few decades DNA has also emerged as an excellent tool for recognition, owing to the hybridization of complementary sequences. Thus, an efficient way to detect a DNA strand is to use its complementary sequence as a probe. Although this works well in solution, it becomes more of a challenge when the probes are arranged on a surface. Chunhai Fan and co-workers at the Shanghai Institute of Applied Physics review recent developments in probe-target recognition processes involving nanostructured-scaffold probes. Such structures have evolved from a single, linear strand of DNA to a single-stranded loop conformation, and into more complex scaffolds such as tetrahedra. The latter offers precise control over the positioning and accessibility of the DNA probes, while preventing adjacent probes from entangling. Along with the rapid merge and development of biotechnology and nanotechnology, various DNA nanostructure scaffolds have been designed, characterized and exploited for a range of applications. Particularly, we have seen the evolution of surface-confined DNA probes with rational design from one-dimensional to two-dimensional and then to three-dimensional, which greatly improve our ability to control the density, orientation and passivation of the surface. In this review, we aim to summarize recent progress on the improvement of probe–target recognition properties by introducing DNA nanostructure scaffolds. A range of new strategies have proven to provide significantly enhanced spatial positioning range and accessibility of the probes on surface over previously reported linear structures. We will also describe applications of DNA nanostructure scaffold-based biosensors.