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Zezhou Liu

Publications and source records attributed to Zezhou Liu.

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DNA Nanostructures Characterized via Dual Nanopore Resensing

DNA nanotechnology uses predictable interactions of nucleic acids to precisely engineer complex nanostructures. Characterizing these self-assembled structures at the single-structure level is crucial for validating their design and functionality. Nanopore sensing is a promising technique for this purpose as it is label-free, solution-based and high-throughput. Here, we present a device that incorporates dynamic feedback to control the translocation of DNA origami structures through and between two nanopores. We observe multiple translocations of the same molecule through the two distinct nanopores as well as measure its time-of-flight between the pores. We use machine learning classification methods in tandem with classical analysis of dwell-time/blockade distributions to analyze the complex multi-translocation events generated by different nanostructures. With this approach, we demonstrate the ability to distinguish DNA nanostructures of different lengths and/or small structural differences, all of which are difficult to detect using conventional, single-nanopore sensing. In addition, we develop a finite element diffusion model of the time-of-flight process and estimate nanostructure size. This work establishes the dual nanopore device as a powerful tool for DNA nanostructure characterization.

physics.bio-ph

DNA Dynamics in Dual Nanopore Tug-of-War

Solid state nanopores have emerged as powerful tools for single-molecule sensing, yet the rapid uncontrolled translocation of the molecule through the pore remains a key limitation. We have previously demonstrated that an active dual-nanopore system, consisting of two closely spaced pores operated via feedback controlled biasing, shows promise in achieving controlled, slowed-down translocation. Translocation control is achieved via capturing the DNA in a special tug-of-war configuration, whereby opposing electrophoretic forces at each pore are applied to a DNA molecule co-captured at the two pores. Here, we systematically explore translocation physics during DNA tug-of-war focusing on genomically relevant longer dsDNA using a T$_4$-DNA model (166\,kbp). We find that longer molecules can be trapped in tug-of-war states with an asymmetric partitioning of contour between the pores. Secondly, we explore the physics of DNA disengagement from a tug-of-war configuration, focusing on the dynamics of DNA free-end escape, in particular how the free-end velocity depends on pore voltage, DNA size and the presence of additional DNA strands between the pores (i.e. arising in the presence of folded translocation). These findings validate theoretical predictions derived from a first passage model and provide new insight into the physical mechanisms governing molecule disengagement in tug-of-war.

cond-mat.soft

Extreme cavity expansion in soft solids: damage without fracture

Cavitation is a common damage mechanism in soft solids. Here, we study this using a phase-separation technique in stretched, elastic solids to controllably nucleate and grow small cavities by several orders of magnitude. The ability to make stable cavities of different sizes, as well as the huge range of accessible strains, allows us to systematically study the early stages of cavity expansion. Cavities grow in a scale-free manner, accompanied by irreversible bond breakage that is distributed around the growing cavity, rather than being localized to a crack tip. Furthermore, cavities appear to grow at constant driving pressure. This has strong analogies with the plasticity that occurs surrounding a growing void in ductile metals. In particular we find that, although elastomers are normally considered as brittle materials, small-scale cavity expansion is more like a ductile process. Our results have broad implications for understanding and controlling failure in soft solids.

cond-mat.soft

Nanopore fabrication via tip-controlled local breakdown using an atomic force microscope

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 we demonstrate the potential of tip controlled dielectric breakdown (TCLB) to fabricate pores 100$\times$ faster, with high scalability and nanometre positioning precision. A conductive atomic force microscope (AFM) tip is brought into contact with a 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, our approach greatly accelerates the electric breakdown process, leading to an average pore fabrication time on the order of 10 ms, at least 2 orders of magnitude shorter than achieved by classic dielectric breakdown approaches. With this fast pore writing speed we can fabricate over 300 pores in half an hour on the same membrane.

physics.bio-ph