Aptamer-functionalized nano-biosensors

Abstract

Nanomaterials have become one of the most interesting sensing materials because of their unique size- and shape-dependent optical properties, high surface energy and surface-to-volume ratio, and tunable surface properties. Aptamers are oligonucleotides that can bind their target ligands with high affinity. The use of nanomaterials that are bioconjugated with aptamers for selective and sensitive detection of analytes such as small molecules, metal ions, proteins, and cells has been demonstrated. This review focuses on recent progress in the development of biosensors by integrating functional aptamers with different types of nanomaterials, including quantum dots, magnetic nanoparticles (NPs), metallic NPs, and carbon nanotubes. Colorimetry, fluorescence, electrochemistry, surface plasmon resonance, surface-enhanced Raman scattering, and magnetic resonance imaging are common detection modes for a broad range of analytes with high sensitivity and selectivity when using aptamer bioconjugated nanomaterials (Apt-NMs). We highlight the important roles that the size and concentration of nanomaterials, the secondary structure and density of aptamers, and the multivalent interactions play in determining the specificity and sensitivity of the nanosensors towards analytes. Advantages and disadvantages of the Apt-NMs for bioapplications are focused.

Keywords: aptamers; biosensors; cells; metal ions; nanomaterials; proteins.

Figure 1.

Schematic representation of colorimetric detection of adenosine. The DNA sequences are shown in the right side of the figure. The A₁₂ in 3′Adap_Au denotes a 12-mer polyadenine chain. In a control experiment, a mutated linker with the two mutations shown by the two short black arrows was used. Reprinted with permission from Reference [32].

Figure 2.

Illustration of the interactions of ATP with Apt-Au NPs and Au NPs. Reprinted with permission from Reference [45].

Figure 3.

Scheme for the engineered cocaine aptamer and the visual detection of cocaine based on the red-to-blue color change of Au NPs. Reprinted with permission from Reference [39].

Figure 4.

(a) Secondary structure of the “8-17” DNAzyme system that consists of an enzyme strand (17E) and a substrate strand (17DS). The cleavage site is indicated by a black arrow. Except for a ribonucleoside adenosine at the cleavage site (rA), all other nucleosides are deoxyribonucleosides. (b) Cleavage of 17DS by 17E in the presence of Pb²⁺. (c) Schematics of DNAzyme-directed assembly of Au NPs and their application as biosensors for metal ions such as Pb²⁺. In this system, the 17DS has been extended on both the 3′ and 5′ ends for 12 bases, which are complementary to the 12-mer DNA attached to the 13-nm gold nanoparticles (DNA_Au). Reprinted with permission from Reference [57].

Figure 5.

Schematic representation of Hg²⁺ nanosensors at various DNA-to-Au NP molar ratios: (a) <30, (b) 30–50, and (c) ≥60. Reprinted with permission from Ref. [51].

Figure 6.

Colorimetric detection of Hg²⁺ using DNA-Au NPs. Reprinted with permission from Ref. [49].

Figure 7.

(a) A scheme showing an electrically modulated fluorescence protein assay including a thrombin-binding aptamer probe grafted on an Au nanowire, the target, a biotinylated thrombin, and the reporter, a fluorophore-labeled streptavidin. (b) Electrical potential applied on the nanowire (top) and modulated fluorescence measured from a sample at a 100 nM thrombin concentration (bottom) are shown synchronously versus time. Reprinted with permission from Ref. [100].

Figure 8.

Schematic representation of the aggregation of Apt-Au NPs in the presence of PDGFs at (a) low, (b) medium, and (c) high concentrations. Reprinted with permission from Reference [126].

Figure 9.

Schematic representations of PDGF nanosensors that operate based on modulation of the fluorescence resonance energy transfer between DMDAP and Apt-Au NPs. Reprinted with permission from Reference [127].

Figure 10.

Schematic representations of PFGF and PDGF-receptor nanosensors that operate based on the modulation of the photoluminescence quenching between PDGF AA-Au NP and Apt-Au NP. h: Planck's constant; ν: frequency of light. Reprinted with permission from Reference [132].