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WIREs Nanomed Nanobiotechnol
Impact Factor: 6.35

Mix‐and‐match nanobiosensor design: Logical and spatial programming of biosensors using self‐assembled DNA nanostructures

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The evergrowing need to understand and engineer biological and biochemical mechanisms has led to the emergence of the field of nanobiosensing. Structural DNA nanotechnology, encompassing methods such as DNA origami and single‐stranded tiles, involves the base pairing‐driven knitting of DNA into discrete one‐, two‐, and three‐dimensional shapes at nanoscale. Such nanostructures enable a versatile design and fabrication of nanobiosensors. These systems benefit from DNA's programmability, inherent biocompatibility, and the ability to incorporate and organize functional materials such as proteins and metallic nanoparticles. In this review, we present a mix‐and‐match taxonomy and approach to designing nanobiosensors in which the choices of bioanalyte and transduction mechanism are fully independent of each other. We also highlight opportunities for greater complexity and programmability of these systems that are built using structural DNA nanotechnology.

This article is categorized under:

  • Implantable Materials and Surgical Technologies > Nanomaterials and Implants
  • Diagnostic Tools > Biosensing
  • Biology‐Inspired Nanomaterials > Nucleic Acid‐Based Structures
  • Nanotechnology Approaches to Biology > Nanoscale Systems in Biology
A schematic representation shows the individual components that comprise a DNA origami nanobiosensor. The binding of the bioanalyte (left) with the ssDNA‐associated bioreceptor (center) on the surface of the DNA origami is transduced as a measurable change in properties (right) that can be recognized and quantified by a detector. Figures in the right column are adapted from Chai, Xie, & Grotewold, ; Chakraborty, Veetil, Ja rey, & Krishnan, ; Michelotti, Johnson‐Buck, Manzo, & Walter, ; Ranjbar & Hafezi‐Moghadam, ; Wang et al., , respectively
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Examples of different transduction mechanisms for DNA origami biosensors. (a) The design (top) and AFM (bottom) image of a PfLDH sensor that transduces the biochemical binding signal to a surface topographical output signal show an example of a protein‐topographical sensor. (Reprinted with permission from Godonoga et al. (). Copyright 2016 Nature Publishing Group) (b) The design (left) and TEM images (right) of DNA origami nanotweezers that change conformation to measure forces between nucleosomes during chromosomal unwinding show an example of a protein‐mechanical sensor. Color scheme: DNA template is shown in yellow, histone octamer is shown in blue, and N‐terminal histone tails are shown in red. The two TEM images show the difference when the nucleosomes attached at different places with respect to the pivot of the spectrometer. (Reprinted with permission from Funke et al. (). Copyright 2016 The Authors) (c) DNA‐PAINT image of a dye‐labeled DNA origami platform (right) comparing to the optical limit (left) shows an example of a nucleic acid‐fluorescence sensor. Scale bar, 100 nm. (Reprinted with permission from Schnitzbauer et al. (). Copyright 2017 Nature Publishing Group) (d) Scheme of using DNA origami as gatekeeper of nanopores shows an example of a nucleic acid‐electrical sensor. This sensor system transduces the chemical signal into ionic current that can be detected in the circuit. (Reprinted with permission from Hernandez‐Ainsa et al. (). Copyright 2013 American Chemical Society) (e) Scheme of the plasmonic walker with two perpendicular gold nanorods (AuNRs) shows an example of a nucleic acid‐plasmonic sensor. As the top NR walks along the origami platform, the chirality of this DNA origami‐based nanostructure changes and change the NR's impact to a polarized light. (Reprinted with permission from Zhou et al. (). Copyright 2015 Nature Publishing Group)
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Examples of different bioanalyte sensing schemes for DNA origami‐based biosensors. (a) The design of a DNA origami box with a controllable lid is an example of a nucleic acid‐mechanical sensor. The lid can be triggered to open by ssDNA “keys” via toehold‐mediated strand exchange. (Reprinted with permission from Andersen et al. (). Copyright 2017 Nature Publishing Group) (b) The scheme of a "synthetic thick filament" DNA nanotube platform decorated with SNAP‐tagged myosin proteins with 14 nm spacing. Fluorescent actin filaments can glide along this structure that is an example of a protein‐fluorescence sensor. (Reprinted with permission from Hariadi et al. (). Copyright 2017 Nature Publishing Group) (c) A bipedal walker that is an example of an ion‐mechanical sensor. The walker can walk along the scaffolds by switching between states A‐D triggered to step forward by Hg2+ or H+ via the formation of the thymine‐Hg‐thymine complex or i‐motif structure, and it can step backwards in the presence of cysteine or OH that disrupts the complex or structure, respectively. (Reprinted with permission from Wang, Elbaz, & Willner (). Copyright 2011 American Chemical Society) (d) The design of a two state nanopliers system that can change states in the presence of ATP is an example of a small molecule‐mechanical sensor. (Reprinted with permission from Walter et al. (). Copyright 2017 American Chemical Society) (e) The schemes for implementing “INH,” “XOR,” “OR,” and “AND” logic gates using nanobiosensors. Each of these logic gates is made by a DNA tetrahedron and can be triggered by two inputs; this is an example of a multianalyte‐fluorescence sensor. “INH” logic gate uses P‐tetra with H+ and OH ions as inputs, the “XOR” logic gate uses PA‐tetra with ATP and OH ions as inputs, “OR” logic gate uses PM‐tetra with Hg2+ and H+ ions as inputs, “AND” logic gate uses H‐tetra with two partially complementary DNA strands (I1, I2) as inputs. (Reprinted with permission from Pei et al. (). Copyright 2012 John Wiley & Sons)
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DNA origami can incorporate features by site‐specifically arraying molecules of interest with nanoscale precision. This capability is unique in the realm of nanomaterials and advance biosensing applications. (a) A scheme for DNA origami‐regulated chemoselective reactions. The biotin‐streptavidin is conjugated to DNA origami with three different linkers. The yellow is noncleavable, the red linkers can be cleaved by DTT, and the green linkers can be cleaved by photogenerated singlet oxygen. (Reprinted with permission from Voigt et al. (). Copyright 2010 Nature Publishing Group) (b) Scheme of a DNA origami‐based molecular system that is spatially addressable at the single‐molecule level. (Top) Singlet oxygen is produced by a positioned 1O2 sensitizer (IPS) at the center and diffuses away to react with the singlet oxygen‐cleavable (SOC) linkers. (Middle) The result of a reaction with one of the SOC linkers is shown. (Bottom) Origami after irradiation and streptavidin addition. The remaining biotins are steptavidin‐bound (yellow balls) indicating spatial control. (Reprinted with permission from Helmig et al. (). Copyright 2010 American Chemical Society) (c) A DNA nanoscale assembly line indicating dynamic motion. The walker (red triangle arrangement) can carry up to four gold nanoparticles (brown dots) as it walks along the DNA origami sheet. (Reprinted with permission from Gu, Chao, Xiao, & Seeman (). 2010 Nature Publishing Group) (d) The design of DNA origami‐based fluorescent barcodes showing diversity and high‐resolution detectability. The main body of the barcode is a DNA nanorod formed by dimerizing two origami monomers. The DNA nanorod consists of four binding zone regions, which are each 113 nm apart. Each binding zone can be decorated by a different combination of fluorophores (shown as blue, red and green segments) to produce the RGB barcode. (Reprinted with permission from Lin et al. (). 2012 Nature Publishing Group)
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Implantable Materials and Surgical Technologies > Nanomaterials and Implants
Nanotechnology Approaches to Biology > Nanoscale Systems in Biology
Diagnostic Tools > Biosensing
Biology-Inspired Nanomaterials > Nucleic Acid-Based Structures

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