Low-Noise Nanopore Enables In-Situ and Label-Free Tracking of a Trigger-Induced DNA Molecular Machine at the Single-Molecular Level

Zhu, Zhentong; Duan, Xiaozheng; Qiao, Li; Wu, Ruiping; Wang, Yesheng; Li, Bingling

doi:10.1021/jacs.0c00029

Cited by 95 publications

(99 citation statements)

References 72 publications

(100 reference statements)

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“…In our previous work, we found that a single short ssDNA or dsDNA protruding out from the carrier is insufficient to induce an obvious second level signal with the ≈14 nm diameter nanopore, [ 24 ] so we placed a DNA three‐way junction (3WJ) in the center to create carrier 1 (Figure 1a, Figure S1a, Supporting Information). [ 25 ] The 3WJ structure on carrier 1 is indeed detectable. About 84% of events showed a clear peak in the middle and gave a second current drop (Δ I ) centered at 0.039 ± 0.001 nA upon a backbone dsDNA level of 0.147 nA (Figure 1c).…”

Section: Resultsmentioning

confidence: 99%

Image Encoding Using Multi‐Level DNA Barcodes with Nanopore Readout

Zhu

Ermann

Chen

et al. 2021

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and readout speed, [11][12][13][14] but it is almost helpless for DNA nanostructure-based storage. Even if the sequence is decoded, it is still difficult to reproduce the whole structure accurately, which indicates the higher security of this storage method from this perspective. Additionally, hardware encryption with physical keys can further improve the security of the information saved by this strategy. [10,15] Solid-state nanopore provides us with a versatile tool to investigate the biomole cules, such as DNA, ribonucleic acid (RNA), and proteins, at the singlemolecule level. [16,17] We recently introduced a solid-state nanopore sensing platform to read bits encoded by 56 DNA hairpins on a 7.2 kb DNA carrier. [18] Readout of the structures required glass nanopores with diameters of around 5 nm. Such a small diameter complicates the fabrication process and reduces the success rates compared to easily manufactured >10 nm glass nanopores. The smaller diameter also leads to more non-specific interaction and pore clogging. [19] In further work, we used a streptavidin-labelled DNA scaffold to build a secure data storage method with binary codes. [15] While protein labels can be used with larger diameter pores, they complicate the molecular assembly and set an upper bound on the data density through their defined size. Additionally, the number of usable protein labels is limited due to the high monovalent salt concentrations required for the readout. The presence of proteins also reduces the lifetime of solid-state nanopores and hence has a detrimental effect on the viability of the readout.In this work, we replace protein barcodes with multi-way DNA junctions to address the shortcoming and limitations of our prior approaches. Inspired by the work of Wang and Seaman [20] we designed a multi-level storage architecture. Building on our established DNA carrier-based rewritable storage system with 14 nm diameter nanopores, [19] we use three DNA junction structures of different sizes (4-way junction, 6-way junction, and 12-way junction) to generate a quaternary encoding system (0-3) on the long linear DNA carrier, which increases the data density compared to classic binary encoding. Through toehold-mediated strand displacement reaction (SDR), [21][22][23] the presence of nanostructures on the carrier can be precisely controlled, allowing data reading and writing. Based on this storage system, we successfully save a grayscale image into the DNA nanostructures on 16 different carriers and read out the information in the mixture. Furthermore, using SDR the image information can be easily encrypted and decrypted.Deoxyribonucleic acid (DNA) nanostructure-based data encoding is an emerging information storage mode, offering rewritable, editable, and secure data storage. Herein, a DNA nanostructure-based storage method established on a solid-state nanopore sensing platform to save and encrypt a 2D grayscale image is proposed. DNA multi-way junctions of different sizes are attached to a double strand of DNA carriers, resulting i...

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Section: Resultsmentioning

confidence: 99%

Image Encoding Using Multi‐Level DNA Barcodes with Nanopore Readout

Zhu

Ermann

Chen

et al. 2021

Small

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“…[6,7] Single molecules techniques, such as nanopore sensors are becoming popular due to their label-free operation, ease of fabrication, the ability of active transportation, and in some cases, the ability to tailor the sensor chemistry via surface modification. [8][9][10][11][12][13][14] Nanopores have been widely used for the detections of nucleic acids, DNA sequencing, [15] and protein sensing. [16][17][18][19][20][21][22][23] However, detection of proteins remains challenging due to fast analyte transport, low capture rates, and the need for relatively high protein concentration.…”

Section: Doi: 101002/smtd202000356mentioning

confidence: 99%

Selective Sensing of Proteins Using Aptamer Functionalized Nanopore Extended Field‐Effect Transistors

et al. 2020

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The ability to sense proteins and protein-related interactions at the singlemolecule level is becoming of increasing importance to understand biological processes and diseases better. Single-molecule sensors, such as nanopores have shown substantial promise for the label-free detection of proteins; however, challenges remain due to the lack of selectivity and the need for relatively high analyte concentrations. An aptamer-functionalized nanopore extended field-effect transistor (nexFET) sensor is reported here, where protein transport can be controlled via the gate voltage that in turn improves single-molecule sensitivity and analyte capture rates. Importantly, these sensors allow for selective detection, based on the choice of aptamer chemistry, and can provide a valuable addition to the existing methods for the analysis of proteins and biomarkers in biological fluids.

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“…Nanopores sensing has shown good potential for a label-free monitoring molecular interaction, identifying structural polymorphisms at the single-molecular level [89]. The pulse modulations in ionic current indicate the target translocation through the nanopore [90].…”

Section: Dna Origami Nanopore Readout Strategymentioning

confidence: 99%

DNA Origami-Enabled Biosensors

Wang

Zhou

et al. 2020

Sensors

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Biosensors are small but smart devices responding to the external stimulus, widely used in many fields including clinical diagnosis, healthcare and environment monitoring, etc. Moreover, there is still a pressing need to fabricate sensitive, stable, reliable sensors at present. DNA origami technology is able to not only construct arbitrary shapes in two/three dimension but also control the arrangement of molecules with different functionalities precisely. The functionalization of DNA origami nanostructure endows the sensing system potential of filling in weak spots in traditional DNA-based biosensor. Herein, we mainly review the construction and sensing mechanisms of sensing platforms based on DNA origami nanostructure according to different signal output strategies. It will offer guidance for the application of DNA origami structures functionalized by other materials. We also point out some promising directions for improving performance of biosensors.

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Low-Noise Nanopore Enables In-Situ and Label-Free Tracking of a Trigger-Induced DNA Molecular Machine at the Single-Molecular Level

Cited by 95 publications

References 72 publications

Image Encoding Using Multi‐Level DNA Barcodes with Nanopore Readout

Image Encoding Using Multi‐Level DNA Barcodes with Nanopore Readout

Selective Sensing of Proteins Using Aptamer Functionalized Nanopore Extended Field‐Effect Transistors

DNA Origami-Enabled Biosensors

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