Specific Biosensing Using DNA Aptamers and Nanopores

Kong, Jinglin; Zhu, Jinbo; Chen, Kaikai; Keyser, Ulrich F.

doi:10.1002/adfm.201807555

Cited by 45 publications

(41 citation statements)

References 43 publications

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“…Recent research has showcased the potential of nanopores to detect molecular features along a DNA carrier strand, including proteins such as anti‐DNA antibodies and streptavidin, single‐stranded versus double‐stranded regions of a molecule, DNA‐hairpins, and aptamers . Potential applications range from digital information storage, multiplexed sensing, and genomic and/or functional genomic applications including genome mapping and epigenetics .…”

Section: Introductionmentioning

confidence: 99%

Flossing DNA in a Dual Nanopore Device

Liu

Zimny

Zhang

et al. 2019

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Recent research has showcased the potential of nanopores to detect molecular features along a DNA carrier strand, including proteins such as anti-DNA antibodies [5] and streptavidin, [6,7] singlestranded versus double-stranded regions of a molecule, [8] DNA-hairpins, [9,10] and aptamers. [11,12] Potential applications range from digital information storage, [9,10] multi plexed sensing, [9,11] and genomic and/or functional genomic applications including genome mapping [13] and epigenetics. [14,15] Solid-state pores in particular can target a more diverse analyte pool than protein pores [16] (e.g., dsDNA, proteins, nucleosomes [17] ) and thereby give access to a broad range of single-molecule applications.A key challenge in performing multilocus sensing of motifs along DNA is the inherent sensitivity of single-molecule systems to noise. Unwanted conformations/ topologies and molecular fluctuations (both equilibrium and nonequilibrium in nature) create systematic and random distortions in the electrical signal pattern of motifs resolved by the sensor. For example, closely spaced features along DNA cannot always be resolved in a given single-molecule read even with state-of-the-art measurements performed with 5 nm diameter nanopores, [10] requiring multiple independent reads from identical copies of different molecules to confidently resolve the features. In addition, the stochastic nature of the translocation process gives rise to broad distributions [18,19] in tag spacings measured across a molecular ensemble; [7] these broad distributions necessitate averaging over additional molecules to obtain precise spacing estimates. A related challenge is providing independent genomic distance calibration along individual single-molecule reads, so that sensor output can be linked to sequence position without a priori knowledge of the distance between motifs. While optics can provide high-resolution spatiotemporal data, [20,21] nanopores can only infer spatial information implicitly from temporal data. In order for nanopore technology to achieve its full potential, it is essential that singlemolecule reads have sufficient quality (e.g., contain sufficiently low systematic and random errors), so that the requirement for further ensemble-level averaging over different molecules is minimized or eliminated. The technology can then be applied to the complex, heterogeneous samples reflective of applications where every molecule may have a different number of bound motifs possessing a distinct spatial distribution.Solid-state nanopores are a single-molecule technique that can provide access to biomolecular information that is otherwise masked by ensemble averaging. A promising application uses pores and barcoding chemistries to map molecular motifs along single DNA molecules. Despite recent research breakthroughs, however, it remains challenging to overcome molecular noise to fully exploit single-molecule data. Here, an active control technique termed "flossing" that uses a dual nanopore device is presented to trap a proteintagged...

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Section: Introductionmentioning

confidence: 99%

Flossing DNA in a Dual Nanopore Device

Liu

Zimny

Zhang

et al. 2019

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“…It consists in the labeling of long DNA strands with spatially controlled markers, giving a specific current signal with recognizable intra-events. The combination of this technique with aptamers has allowed the detection of ATP [ 169 , 170 ] and proteins [ 157 , 170 ]. In 2017, a double-stranded DNA scaffold assembly with an aptamer protrusion has been used for the specific detection of ATP [ 169 ].…”

Section: Nanopores and Aptamers: A Winning Combinationmentioning

confidence: 99%

“…Finally, they performed this strategy in human serum, demonstrating the flexibility and the efficiency of this bar-coding aptamer detection even in complex sample. Another study has shown the feasibility of using this technique for the simultaneous detection of three different targets on the DNA carrier: ATP, thrombin and lysozyme [ 170 ].…”

Section: Nanopores and Aptamers: A Winning Combinationmentioning

confidence: 99%

Sensing with Nanopores and Aptamers: A Way Forward

Reynaud

Bouchet-Spinelli

Raillon

et al. 2020

Sensors

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In the 90s, the development of a novel single molecule technique based on nanopore sensing emerged. Preliminary improvements were based on the molecular or biological engineering of protein nanopores along with the use of nanotechnologies developed in the context of microelectronics. Since the last decade, the convergence between those two worlds has allowed for biomimetic approaches. In this respect, the combination of nanopores with aptamers, single-stranded oligonucleotides specifically selected towards molecular or cellular targets from an in vitro method, gained a lot of interest with potential applications for the single molecule detection and recognition in various domains like health, environment or security. The recent developments performed by combining nanopores and aptamers are highlighted in this review and some perspectives are drawn.

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“…The DNA strands were then analyzed by similar protein encoded DNA carriers. [ 132 ] Overall, digitally encoded DNA carrier shows great potential in selective and multiplexed detection of proteins, since only 10 bits enable coding 2 10 = 1024 proteins. However, the molecule weight contrast between the binding site and the target analyte should be large enough to distinguish bound and unbound target.…”

Section: Selectivitymentioning

confidence: 99%

Four Aspects about Solid‐State Nanopores for Protein Sensing: Fabrication, Sensitivity, Selectivity, and Durability

Tong

Zhao

2020

Adv Healthcare Materials

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Solid‐state nanopores are a mimic of innate biological nanopores embedded on lipid membranes. They are fabricated on thin suspended layers of synthetic materials that provide superior thermal, mechanical, chemical stability, and geometry flexibility. As their counterpart biological nanopores reach the goal of DNA sequencing and become commercial, solid‐state nanopores thrive in aspects of protein sensing and have become an important research component for clinical diagnostic technologies. This review focuses on resistive pulse sensing modes, which are versatile for low‐cost, portable sensing devices and summarizes four main aspects toward commercially available resistive pulse‐based protein sensing techniques using solid‐state nanopores. In each aspect of fabrication, sensitivity, selectivity, and durability, brief fundamentals are introduced and the challenges and improvements are discussed. The rapid advance of a practical technique requires greater multidisciplinary cooperation. The review aims at clarifying existing obstacles in solid‐state nanopore based protein sensing, intriguing readers with existing solutions and finally encouraging multidisciplinary researchers to advance the development of this promising protein sensing methodology.

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Specific Biosensing Using DNA Aptamers and Nanopores

Cited by 45 publications

References 43 publications

Flossing DNA in a Dual Nanopore Device

Flossing DNA in a Dual Nanopore Device

Sensing with Nanopores and Aptamers: A Way Forward

Four Aspects about Solid‐State Nanopores for Protein Sensing: Fabrication, Sensitivity, Selectivity, and Durability

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