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In combining DNA nanotechnology and high-bandwidth single-molecule detection in nanopipettes, we demonstrate an all-electric, label-free hybridisation sensor for short DNA sequences (< 100 nt). Such short fragments are known to occur as circulating cell-free DNA in various bodily fluids, such as blood plasma and saliva, and have been identified as disease markers for cancer and infectious diseases. To this end, we use as a model system a 88-mer target from the RV1910c gene in Mycobacterium tuberculosis that is associated with antibiotic (isoniazid) resistance in TB. Upon binding to short probes attached to long carrier DNA, we show that resistive pulse sensing in nanopipettes is capable of identifying rather subtle structural differences, such as the hybridisation state of the probes, in a statistically robust manner. With significant potential towards multiplexing and high-throughput analysis, our study points towards a new, single-molecule DNA assay technology that is fast, easy to use and compatible with point of care environments.
We report a theoretical study of DNA flexibility and quantitatively predict the ring closure probability as a function of DNA contour length. Recent experimental studies show that the flexibility of short DNA fragments (as compared to the persistence
Single molecule force spectroscopy of DNA strands adsorbed at surfaces is a powerful technique used in air or liquid environments to quantify their mechanical properties. Although the force responses are limited to unfolding events so far, single bas
Dielectrophoresis can potentially be used as an efficient trapping tool in the fabrication of molecular devices. For nanoscale objects, however, the Brownian motion poses a challenge. We show that the use of carbon nanotube electrodes makes it possib
In living cells, proteins combine 3D bulk diffusion and 1D sliding along the DNA to reach a target faster. This process is known as facilitated diffusion, and we investigate its dynamics in the physiologically relevant case of confined DNA. The confi
The pair interaction between two stiff parallel linear DNA molecules depends not only on the distance between their axes but on their azimuthal orientation. The positional and orientational order in columnar B-DNA assemblies in solution is investigat