Scaffolded biosensors with designed DNA nanostructures

Abstract

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 probetarget 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. INTRODUCTIONDetection of nucleic acids (DNA or RNA) is an integral step in many applications, including in clinical diagnosis, environmental monitoring and antibioterrorism. 1 With these applications in mind, significant efforts have been made to develop sensitive, selective, rapid and cost-effective DNA (or RNA) biosensors. In parallel, DNAbased devices have also attracted a significant, recent interest owing to their promising applications in nanoelectronics, 2,3 biomolecular computations, 4-8 cellular imaging 9 and drug delivery. [10][11][12] In a typical design of DNA biosensors and nanodevices, oligonucleotides are often used as the molecular recognition layer. Because DNA is comprised of only four bases with A-T and G-C pairing, DNA hybridization processes are highly predictable and can be finely tuned with a rational design of the sequence. In addition, DNA oligonucleotides are usually easy to design, chemically stable and cost-effective.Understanding the physical structure of a DNA probe immobilized on a surface is critical in applications using DNA as a molecular recognition element. The properties of the DNA molecular recognition layer (such as selectivity, sensitivity and reproducibility) highly depend on the structure of the self-assembled DNA film. Modeling studies with thiolated DNA have demonstrated that efficient hybridization occurs in the well-controlled condition of surface-attached probes with large interprobe distances and upright conformations. [13][14][15][16][17][18][19][20][21][22][23][24]

Incorporating ATP into biomimetic catalysts for realizing exceptional enzymatic performance over a broad temperature range

“…37 In addition, ATP could bind to an in vitro-selected Enzymatic performance of ATP over a broad temperature range Y Lin et al 27-base anti-ATP aptamer with high affinity and could induce the aptamer to undergo a conformational change from random coil to tertiary structure. 40 Inspired by the unique properties of ATP, we found that ATP could promote the catalytic activity of the Au-SiO 2 catalyst within a fairly broad range of operating temperatures (Figures 2b and c). As shown in Figure 2c, the activity of the nanocatalyst shows a linear increase along with the temperature elevation from 25 to 85 1C, and this is in sharp contrast to that obtained without ATP (Figures 2a and c) and to that of the HRP enzyme (Supplementary Figure S5).…”

Polymerase/nicking enzyme synergetic isothermal quadratic DNA machine and its application for one-step amplified biosensing of lead (II) ions at femtomole level and DNA methyltransferase

“…As a universal sensing system, this DNA machine can be readily constructed to be an electrochemical or electrochemiluminescence biosensor by only changing the signal unit (MB in this work) to corresponding signal reporters (electrochemical MB or electrochemiluminescence MB). 39,40 Our ongoing work will demonstrate the applicability of this ESQM-based electrochemical biosensor combined with DNA nanostructure in the detection of cancer biomarkers such as microRNA and DNA methylation. …”

Emerging applications of label-free optical biosensors

“…Indeed, DNA is increasingly used to create nano-scaffolds on surfaces for controlling probe density, position, and accessibility with nanometric resolution [87], hence enabling to minimize the effect of competing interaction with the surface. Furthermore, selected sequences can act as aptamers capable of binding specific targets, ranging from metal ions [88] to proteins [72,89].…”