Probing DNA Translocations with Inplane Current Signals in a Graphene Nanoribbon with a Nanopore

Many theoretical studies predict that DNA sequencing should be feasible by monitoring the transverse current through a graphene nanoribbon while a DNA molecule translocates through a nanopore in that ribbon. Such a readout would benefit from the special transport properties of graphene, provide ultimate spatial resolution because of the single-atom layer thickness of graphene, and facilitate high-bandwidth measurements. Previous experimental attempts to measure such transverse inplane signals were however dominated by a trivial capacitive response. Here, we explore the feasibility of the approach using a custom-made differential current amplifier that discriminates between the capacitive current signal and the resistive response in the graphene. We fabricate well-defined short and narrow (30 nm × 30 nm) nanoribbons with a 5 nm nanopore in graphene with a high-temperature scanning transmission electron microscope to retain the crystallinity and sensitivity of the graphene. We show that, indeed, resistive modulations can be observed in the graphene current due to DNA translocation through the nanopore, thus demonstrating that DNA sensing with inplane currents in graphene nanostructures is possible. The approach is however exceedingly challenging due to low yields in device fabrication connected to the complex multistep device layout.BN/Cees Dekker LabQN/Zandbergen LabGenera

Label-Free Optical Detection of DNA Translocations through Plasmonic Nanopores

Solid-state nanopores are single-molecule sensors that hold great potential for rapid protein and nucleic-acid analysis. Despite their many opportunities, the conventional ionic current detection scheme that is at the heart of the sensor suffers inherent limitations. This scheme intrinsically couples signal strength to the driving voltage, requires the use of high-concentration electrolytes, suffers from capacitive noise, and impairs high-density sensor integration. Here, we propose a fundamentally different detection scheme based on the enhanced light transmission through a plasmonic nanopore. We demonstrate that translocations of single DNA molecules can be optically detected, without the need of any labeling, in the transmitted light intensity through an inverted-bowtie plasmonic nanopore. Characterization and the cross-correlation of the optical signals with their electrical counterparts verify the plasmonic basis of the optical signal. We demonstrate DNA translocation event detection in a regime of driving voltages and buffer conditions where traditional ionic current sensing fails. This label-free optical detection scheme offers opportunities to probe native DNA-protein interactions at physiological conditions.BN/Cees Dekker LabQN/Kuipers LabQN/Quantum Nanoscienc

Circular Dichroism Measurement of Single Metal Nanoparticles Using Photothermal Imaging

Circular dichroism (CD) spectroscopy is a powerful optical technique for the study of chiral materials and molecules. It gives access to an enantioselective signal based on the differential absorption of right and left circularly polarized light, usually obtained through polarization analysis of the light transmitted through a sample of interest. CD is routinely used to determine the secondary structure of proteins and their conformational state. However, CD signals are weak, limiting the use of this powerful technique to ensembles of many molecules. Here, we experimentally realize the concept of photothermal circular dichroism, a technique that combines the enantioselective signal from circular dichroism with the high sensitivity of photothermal microscopy, achieving a superior signal-to-noise ratio to detect chiral nano-objects. As a proof of principle, we studied the chiral response of single plasmonic nanostructures with CD in the visible range, demonstrating a signal-to-noise ratio better than 40 with only 30 ms integration time for these nanostructures. The high signal-to-noise ratio allows us to quantify the CD signal for individual nanoparticles. We show that we can distinguish relative absorption differences for right circularly and left circularly polarized light as small as gmin = 4 × 10-3 for a 30 ms integration time with our current experimental settings. The enhanced sensitivity of our technique extends CD studies to individual nano-objects and opens CD spectroscopy to numbers of molecules much lower than those in conventional experiments.QN/Kuipers LabQN/Quantum Nanoscienc

Direct observation of DNA knots using a solid-state nanopore

Long DNA molecules can self-entangle into knots. Experimental techniques for observing such DNA knots (primarily gel electrophoresis) are limited to bulk methods and circular molecules below 10 kilobase pairs in length. Here, we show that solid-state nanopores can be used to directly observe individual knots in both linear and circular single DNA molecules of arbitrary length. The DNA knots are observed as short spikes in the nanopore current traces of the traversing DNA molecules and their detection is dependent on a sufficiently high measurement resolution, which can be achieved using high-concentration LiCl buffers. We study the percentage of molecules with knots for DNA molecules of up to 166 kilobase pairs in length and find that the knotting occurrence rises with the length of the DNA molecule, consistent with a constant knotting probability per unit length. Our experimental data compare favourably with previous simulation-based predictions for long polymers. From the translocation time of the knot through the nanopore, we estimate that the majority of the DNA knots are tight, with remarkably small sizes below 100 nm. In the case of linear molecules, we also observe that knots are able to slide out on application of high driving forces (voltage).Accepted Author ManuscriptBN/Cees Dekker LabBN/Technici en AnalistenEducation and Student Affair