DNA is a free-draining polymer. This subtle but "unfortunate" property of highly charged polyelectrolytes makes it impossible to separate nucleic acids by free-flow electrophoresis. This is why one must typically use a sieving matrix, such as a gel or an entangled polymer solution, in order to obtain some electrophoretic size separation. An alternative approach consists of breaking the charge to friction balance of free-draining DNA molecules. This can be achieved by labeling the DNA with a large, uncharged molecule (essentially a hydrodynamic parachute, which we also call a drag-tag) prior to electrophoresis; the resulting methodology is called end-labeled free-solution electrophoresis (ELFSE). In this article, we review the development of ELFSE over the last decade. In particular, we examine the theoretical concepts used to predict the ultimate performance of ELFSE for single-stranded (ssDNA) sequencing, the experimental results showing that ELFSE can indeed overcome the free-draining issue raised above, and the technological advances that are needed to speed the development of competitive ELFSE-based sequencing and separation technologies. Finally, we also review the reverse process, called free-solution conjugate electrophoresis (FSCE), wherein uncharged polymers of different sizes can be analyzed using a short DNA molecule as an electrophoretic engine.

The aim of the present work is to investigate by molecular dynamics (MD) calculations the interaction between a moving edge dislocation in an -Fe crystal and a copper precipitate. In the absence of external stresses, two edge dislocations with the same slip plane and opposite Burgers vectors within a perfect -Fe crystal lattice are investigated. In agreement with Frank's rule, the movement of the dislocations under mutual attraction is found and attention is focused on the interaction between one of the dislocations and the Cu precipitate. The critical resolved shear stress of the Fe was calculated and the influence of different sizes of Cu precipitates on the dislocation mobility was studied. The pinning of the dislocation line at the Cu inclusion as derived from the atomistic modelling agrees with previously published continuum theoretical behaviour of pinned dislocations. Therefore, nanosimulation as a way to model precipitation hardening could be established as a useful scientific tool.

In the framework of the classical blob theory of end-labeled free-solution electrophoresis of ssDNA, and based on recent experimental data with linear and branched polymeric labels (or drag-tags), the present study puts forward design principles for the optimal type of branching that would give, for a given total number of monomers, the highest effective frictional drag for ssDNA sequencing purposes. The hydrodynamic radii of the linear and branched labels are calculated using standard models like the freely jointed chain model and the Kratky-Porod worm-like chain model. Based on comparisons of the theory with the experimental data, we propose that the design of new branched labels should use either side chains whose length is comparable to the distance between the branching points or two long branches located near the ends of the molecule's backbone.

In this paper we propose an electrode design and a switching pattern of the applied DC electrode potentials for a microfluidic device to be used in size separation of DNA molecules. Estimates on the separation resolution, which are based on numerical solutions of a Newton-type equation on time-averaged quantities, are presented for an input batch sample of DNA fragments with sizes up to 220 base pairs (bp). The active area of the device (which can be microfabricated by standard photolitographic techniques) is a channel 6 µm wide, 8 µm deep and 150 µm in length, flanked by 23 plane parallel integrated electrodes, individually addressed with low DC voltages, up to ± 25 V. In the active area a time-dependent non-uniform electric field, or a travelling dielectrophoretic wave (TDW) is being produced. In order to enhance the separation resolution, the polarization DC potentials are switched with a relatively high frequency (≈ 10−7 s), which is chosen accordingly with the buffer conductivity and dielectric constants of the fluid and particles. Since the external field is of DC type, we put forward an explanatory model of the dielectric response of the DNA to the time-dependent applied field. We then numerically investigate the size-dependent response of the DNA in a low conductivity buffer (≈0.01 Ω−1 m−1) under the influence of the electric field, which is calculated by means of the method of moments. The results of the computer modelling indicate the existence of a threshold value for the size of the successfully transported molecules, which can be adjusted by varying the velocity of the dielectrophoretic wave produced by the system. The estimated error in selecting a chosen group of molecules with sizes above a specified value is about 5 bp, while the processing times are of the order of hundred of seconds.

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