Assembly and Application of DNA Origami-based Fluorescence Arrays

Abstract

Organic fluorescent molecules with excellent optical properties such as small size and high brightness, are widely used in the field of bioimaging and target molecule detection. Compared to monodispersed fluorescent molecules, fluorescence arrays provide spatial controllability and quantitative programmability for patterning fluorescent molecules, which open new possibilities for expanding the applications of fluorescent molecules. The development of DNA origami techniques allows sub-nanometer addressing capabilities, which is the structural basis for organizing molecules at designed positions. DNA single strands form duplex through complementary pairing, which provides simplicity, efficiency and high orthogonality for construction and diverse programming of fluorescence arrays on DNA origami. Meanwhile, the flexible design of DNA origami provides abundant templates for one-dimensional, two-dimensional and three-dimensional fluorescence arrays of different shapes, making it widely used as a platform for building nanoscale spatial molecular arrays. The characterization of topography on DNA origami tremendously relies on atomic force microscopy (AFM). However, fluorescent molecules on DNA origami usually do not introduce significant topographical change, therefore, cannot be observed well using AFM. Recently developed DNA-PAINT (point accumulation for imaging in nanoscale topography) super-resolution imaging method is based on transient interactions between DNA oligos, which realize the characterization of nanoscale structures by fluorescent imaging. It is a new routine for the characterization of the fluorescence arrays on origami. The development of detectors such as EMCCD and CMOS also provides a higher time resolution for the detection of fluorescent signals, facilitating more accurate dynamic study of interaction between molecules In this review, we summarize recent research progress on the DNA origami-based fluorescence arrays. We introduced the design and assembly principle of DNA origami as template for patterning fluorescent dyes, and reviewed the existing strategies for the construction of fluorescence arrays on DNA origami with different shapes. Then we discribe the characterization techniques of DNA origami-based fluorescence arrays, focusing on recently developed super−resolution imaging. Furthermore, we introduced the application of DNA origami-based fluorescence arrays in bioimaging, biosensing and diagnostics. We highlighted the fundamental biochemical properties of the fluorescence arrays, such as designable topography, quantized fluorescence intensity and localized reaction and summarized the progress routes and challenges in the fundamental study and applications of DNA origami-based fluorescence arrays. Finally, we offered a perspective on the roadmap of DNA origami-based fluorescence arrays as follows: (1) the fixed relative positions of each fluorescent molecule in the array could provide information for mechanical tests. (2) Combination of fluoresecen arrays with biocomputing could also be an important application direction. (3) Due to the variety of modifications of DNA molecules, fluorescence arrays can be combined with other functional molecules to develop multifunctional fluorescence arrays for in - situ intelligent regulation while performing imaging.