Optical sensing and analyte manipulation in solid-state nanopores

Gilboa, Tal; Meller, A.

doi:10.1039/c4an02388a

Cited by 78 publications

(78 citation statements)

References 79 publications

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“…For biological nanopores, a DNA-translocating motor protein (such as a helicase or polymerase) has been used to slowly feed a ssDNA strand into a protein pore for DNA sequencing [13][14][15] . For solid-state nanopores fabricated in thin SiNx membranes [16][17][18] or 2D materials (graphene [19][20][21] , boron nitride [22][23][24] , molybdenum disulfide [25][26][27] ), various efforts have been made to either increase time resolution 16,17,[28][29][30][31] , or slow down the translocation process 32 by the use of ionic liquids 27 , pore surface engineering 33 , mechanical manipulation with a double pore system 34 , and optical trapping 35 . Nevertheless, the SNR has not yet allowed de novo DNA sequencing with solid-state pores.…”

Section: Introductionmentioning

confidence: 99%

Comparing current noise in biological and solid-state nanopores

Fragasso

Schmid

Dekker

2019

Preprint

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Nanopores bear great potential as single-molecule tools for bioanalytical sensing and sequencing, due to their exceptional sensing capabilities, high-throughput, and low cost. The detection principle relies on detecting small differences in the ionic current as biomolecules traverse the nanopore. A major bottleneck for the further progress of this technology is the noise that is present in the ionic current recordings, because it limits the signal-to-noise ratio and thereby the effective time resolution of the experiment. Here, we review the main types of noise at low and high frequencies and discuss the underlying physics. Moreover, we compare biological and solid-state nanopores in terms of the signal-to-noise ratio (SNR), the important figure of merit, by measuring free translocations of a short ssDNA through a selected set of nanopores under typical experimental conditions. We find that SiNx solid-state nanopores provide the highest SNR, due to the large currents at which they can be operated and the relatively low noise at high frequencies. However, the real game-changer for many applications is a controlled slowdown of the translocation speed, which for MspA was shown to increase the SNR >160-fold. Finally, we discuss practical approaches for lowering the noise for optimal experimental performance and further development of the nanopore technology.

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Section: Introductionmentioning

confidence: 99%

Comparing current noise in biological and solid-state nanopores

Fragasso

Schmid

Dekker

2019

Preprint

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“…Furthermore, the localized electromagnetic field is strongly enhanced at the nanoantenna, which creates routes for optical readout, such as surface‐enhanced fluorescence and surface‐enhanced Raman spectroscopy that can complement the traditional ionic current readout. Nanopore sensing will benefit from optical readout strategies as detection schemes allow for low‐noise acquisition at high bandwidth and optical signals can carry rich information about the chemical composition of the analyte …”

mentioning

confidence: 99%

“…[4] Furthermore, the localized electromagnetic field is strongly enhanced at the nanoantenna, which creates routes for optical readout, such as surface-enhanced fluorescence [5] and surface-enhanced Raman spectroscopy [6] that can complement the traditional ionic current readout. Nanopore sensing will benefit from optical readout strategies as detection schemes allow for lownoise acquisition at high bandwidth [7] and optical signals can carry rich information about the chemical composition of the analyte. [8] Plasmonic-nanogap-based structures are a superior class of plasmonic nanoantennas as they can generate extremely localized electromagnetic-field (|E| 2 ) enhancements of up to 10 4 [9] when the gap mode is excited.…”

mentioning

confidence: 99%

Integrating Sub‐3 nm Plasmonic Gaps into Solid‐State Nanopores

Shi

Verschueren

Pud

et al. 2017

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Plasmonic nanopores combine the advantages of nanopore sensing and surface plasmon resonances by introducing confined electromagnetic fields to a solid-state nanopore. Ultrasmall nanogaps between metallic nanoantennas can generate the extremely enhanced localized electromagnetic fields necessary for single-molecule optical sensing and manipulation. Challenges in fabrication, however, hamper the integration of such nanogaps into nanopores. Here, we report a top-down approach for integrating a plasmonic antenna with an ultrasmall nanogap into a solid-state nanopore. Employing a two-step e-beam lithography process, we demonstrate the reproducible fabrication of nanogaps down to a sub-1nm scale. Subsequently, nanopores were drilled through the 20 nm SiN membrane at the center of the nanogap using focused-electron-beam sculpting with a transmission electron microscope, at the expense of a slight gap expansion for the smallest gaps. Using this approach, sub-3nm nanogaps can be readily fabricated on solid-state nanopores. We show the functionality of these plasmonic nanopores for single-molecule detection by performing DNA translocations. These integrated devices can generate intense electromagnetic fields at the entrance of the nanopore and can be expected to find applications in nanopore-based single-molecule trapping and optical sensing.

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“…The baseline (black) and five times rms noise (green) of the recorded current signal filtered at 50 kHz define the detection threshold of the translocation events. The nanopores in both chip materials had a diameter of 17 nm and were made by controlled breakdown [49]. Figure 3 also shows that with identical protein concentration in the recording electrolyte above the nanopore chip, the current trace filtered at 50 kHz from the fused silica chip detected translocation events four-times more frequently than the one from the silicon chip.…”

Section: Protein Translocations With a Silicon Chip And A Fused Silicmentioning

confidence: 94%

Wafer-scale fabrication of fused silica chips for low-noise recording of resistive pulses through nanopores

et al. 2019

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This paper presents a maskless method to manufacture fused silica chips for low-noise resistivepulse sensing. The fabrication includes wafer-scale density modification of fused silica with a femtosecond-pulsed laser, low-pressure chemical vapor deposition (LPVCD) of silicon nitride (SiN x ) and accelerated chemical wet etching of the laser-exposed regions. This procedure leads to a freestanding SiN x window, which is permanently attached to a fused silica support chip and the resulting chips are robust towards Piranha cleaning at ∼80°C. After parallel chip manufacturing, we created a single nanopore in each chip by focused helium-ion beam or by controlled breakdown. Compared to silicon chips, the resulting fused silica nanopore chips resulted in a four-fold improvement of both the signal-to-noise ratio and the capture rate for signals from the translocation of IgG 1 proteins at a recording bandwidth of 50 kHz. At a bandwidth of ∼1 MHz, the noise from the fused silica nanopore chips was three-to six-fold reduced compared to silicon chips. In contrast to silicon chips, fused silica chips showed no laser-induced current noise-a significant benefit for experiments that strive to combine nanopore-based electrical and optical measurements.

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Optical sensing and analyte manipulation in solid-state nanopores

Cited by 78 publications

References 79 publications

Comparing current noise in biological and solid-state nanopores

Comparing current noise in biological and solid-state nanopores

Integrating Sub‐3 nm Plasmonic Gaps into Solid‐State Nanopores

Wafer-scale fabrication of fused silica chips for low-noise recording of resistive pulses through nanopores

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