Length-independent DNA packing into nanopore zero-mode waveguides for low-input DNA sequencing

Larkin, Joseph; Henley, Robert Y.; Jadhav, Vivek; Korlach, Jonas; Wanunu, Meni

doi:10.1038/nnano.2017.176

Cited by 109 publications

(104 citation statements)

References 42 publications

(50 reference statements)

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“…Nanopores are essential in biology and play an important role in shuttling biomolecules between membrane compartments and cells. [1][2][3][4][5][6][7] Outside biology, nanopores have achieved a break-through in portable DNA sequencing 8,9 and additionally found widespread use as tools to detect and characterize individual molecules or nanoparticles. [10][11][12][13][14][15][16][17][18][19][20] The underlying sensing principle relies on the passage of individual objects through an electrolyte-filled pore that leads to transient detectable changes in electrical read-out.…”

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confidence: 99%

Defined Bilayer Interactions of DNA Nanopores Revealed with a Nuclease-Based Nanoprobe Strategy

Burns

Howorka

2018

ACS Nano

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DNA nanopores are a recent class of bilayer-puncturing nanodevices that can help advance biosensing, synthetic biology, and nanofluidics. Here, we create archetypal lipid-anchored DNA nanopores and characterize them with a nanoprobe-based approach to gain essential information about their interactions with bilayers. The strategy determines the molecular accessibility of DNA pores with a nuclease and can thus distinguish between the nanopores' membrane-adhering and membrane-spanning states. The analysis reveals, for example, that pores interact with bilayers in two steps whereby fast initial membrane tethering is followed by slower reorientation to the puncturing state. Tethering occurs for pores with one anchor, while puncturing requires multiple anchors. Both low and high-curvature membranes are good substrates for tethering, but efficient insertion proceeds only for high-curvature bilayers of the examined lipid composition. This is likely due to the localized lipid misalignments and the associated lower energetic barrier for pore permeation. Our study advances the fields of DNA nanotechnology and nanopores by overcoming the considerable experimental hurdle of efficient membrane insertion. It also provides mechanistic insights to aid the design of advanced nanopores, and offers a useful route to probe bilayer orientation of DNA nanostructures.

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confidence: 99%

Defined Bilayer Interactions of DNA Nanopores Revealed with a Nuclease-Based Nanoprobe Strategy

Burns

Howorka

2018

ACS Nano

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“…The choice of model depends on the application; for instance spectroscopy does not demand a fast real-time output but accurate and precise estimations. There are other applications especially in biology, for instance in DNA sequencing, 66 where the accuracy of the peak wavelength is not of importance as long as it is estimated close enough, but the time is of vital importance. training samples).…”

Section: Discussionmentioning

confidence: 99%

Development of use-specific high-performance cyber-nanomaterial optical detectors by effective choice of machine learning algorithms

Hejazi

Liu

Farnoosh

et al. 2020

Mach. Learn.: Sci. Technol.

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P( |T) (nm) Unknown Narrow-Band Light arXiv:1912.11751v3 [physics.app-ph] 3 Jan 2020 term reliability can be equal or more important considerations. Although various machine learning (ML) tools are frequently used on sensor and detector networks to address these considerations and dramatically enhance their functionalities, nonetheless, their effectiveness on nanomaterials-based sensors has not been explored. Here, we show that the best choice of ML algorithm in a cyber-nanomaterial detector is largely determined by the specific useconsiderations, including accuracy, computational cost, speed, and resilience against drifts and long-term ageing effects. When sufficient data and computing resources are provided, the highest sensing accuracy can be achieved by the k-nearest neighbors (kNN) and Bayesian inference algorithms, however, these algorithms can be computationally expensive for real-time applications. In contrast, artificial neural networks (ANN) are computationally expensive to train (off-line), but they provide the fastest result under testing conditions (on-line) while remaining reasonably accurate. When access to data is limited, support vector machines (SVMs) can perform well even with small training sample sizes, while other algorithms show considerable reduction in accuracy if data is scarce, hence, setting a lower limit on the size of required training data. We also show by tracking and modeling the long-term drifts of the detector performance over large (i.e. one year) time-frame, it is possible to dramatically improve the predictive accuracy without the need for any recalibration. Our research shows for the first time that if the ML algorithm is chosen specific to the use-case, lowcost solution-processed cyber-nanomaterial detectors can be practically implemented under diverse operational requirements, despite their inherent variabilities.

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“…Plasmonic devices with interfaced pores require positioning pores at the optimal distance (10–20 nm) from nanoantennas in order to maximize plasmonic coupling . In devices utilizing nanofluidic confinement (e.g., nanochannels, nanocavities) pores need to be aligned with etched sub 100 nm features . In addition to producing pores, our AFM based approach can exploit multiple scanning modalities (topographic, chemical, electrostatic) to map the device prior to pore production and so align pores precisely to existing features.…”

Section: Discussionmentioning

confidence: 99%

Nanopore Formation via Tip‐Controlled Local Breakdown Using an Atomic Force Microscope

et al. 2019

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The dielectric breakdown approach for forming nanopores has greatly accelerated the pace of research in solid‐state nanopore sensing, enabling inexpensive formation of nanopores via a bench top setup. Here the potential of tip‐controlled local breakdown (TCLB) to fabricate pores 100× faster, with high scalability and nanometer positioning precision using an atomic force microscope (AFM) is demonstrated. A conductive AFM tip is brought into contact with a silicon nitride membrane positioned above an electrolyte reservoir. Application of a voltage pulse at the tip leads to the formation of a single nanoscale pore. Pores are formed precisely at the tip position with a complete suppression of multiple pore formation. In addition, the approach greatly accelerates the electric breakdown process, leading to an average pore fabrication time on the order of 10 ms, at least two orders of magnitude shorter than achieved by classic dielectric breakdown approaches. With this fast pore writing speed over 300 pores can be fabricated in half an hour on the same membrane.

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Length-independent DNA packing into nanopore zero-mode waveguides for low-input DNA sequencing

Cited by 109 publications

References 42 publications

Defined Bilayer Interactions of DNA Nanopores Revealed with a Nuclease-Based Nanoprobe Strategy

Defined Bilayer Interactions of DNA Nanopores Revealed with a Nuclease-Based Nanoprobe Strategy

Development of use-specific high-performance cyber-nanomaterial optical detectors by effective choice of machine learning algorithms

Nanopore Formation via Tip‐Controlled Local Breakdown Using an Atomic Force Microscope

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