Separation of DNA by length in rotational flow: Lattice-Boltzmann-based simulations

Abstract

We use a lattice-Boltzmann based Brownian dynamics simulation to investigate the separation of different lengths of DNA through the combination of a trapping force and the microflow created by counter-rotating vortices. We can separate most long DNA molecules from shorter chains that have lengths differing by as little as 30%. The sensitivity of this technique is determined by the flow rate, size of the trapping region, and the trapping strength. We expect that this technique can be used in microfluidic devices to separate long DNA fragments that result from techniques such as restriction enzyme digests of genomic DNA. V C 2015 AIP Publishing LLC.[http://dx.doi.org/10.1063/1.4926667] The development of novel methods for manipulating biopolymers such as DNA is required for the continued advancement of microfluidic devices. Techniques such as restriction enzyme digests for genomic sequencing rely on the detection of DNA that differ in length by sometimes thousands of base pairs. 1 Methods that separate DNA strands with resolutions on the order of kilobase pairs are required to analyze the products of this technique. To gain an insight into possible techniques to separate polymers, it can be helpful to review the methods to separate particles in microfluidic devices. Experimental work has shown how hydrodynamic mechanisms can lead to separation of particles based on size and deformability. 2 Eddies, microvortices, and hydrodynamic tweezers have been used to trap and sort particles. The mechanism of the trapping and sorting arises from the differences between interactions of the particles with the fluid. [2][3][4][5][6][7][8] In particular, counter-rotating vortices have been used to sort particles and manipulate biopolymers. They have been used to deposit DNA precisely across electrodes 9 and trap DNA. 10,11 Vortex flow may therefore be a good basis for a technique for sorting DNA by length.Streaming flow has been used in experiments to separate colloids of different size. Previous work on DNA has shown that counter-rotating vortices can be used to trap DNA dynamically. Long strands of DNA have been observed to stretch between the centers of two counter-rotating vortices. The polymer stays trapped in this state for significant amounts of time. 12 In a different experiment, the vortices were used to thermally cycle the polymer and allow replication via the polymerase chain reaction (PCR). The DNA is also trapped against one wall by a thermophoretic force in these experiments. 10 The strength of the trap is controlled by the gradient in temperature created by a focused infrared laser beam.Trapping DNA at one wall by counter-rotating vortices has also been explored in simulation and found to depend on the Peclet number, Pe ¼ u max L/D m , where u max is the maximum speed of the vortex, L is the box size, and D m is the diffusion coefficient of one bead in the

Mesoscopic simulations at the physics-chemistry-biology interface

“…Computer simulations have the ability to access the fine details of the translocation process, both for technological innovations and for a better understanding of the biological processes involving the migration of small biopolymers. Consequently, various applications of LBPD have also appeared in recent years [103][104][105][106][107].…”

Computational Studies of DNA Separations in Micro-Fabricated Devices: Review of General Approaches and Recent Applications

“…LBM was also used in a study on the translocation of DNA through nanopores [76] and in the calculation of rotational flow fields for DNA separation simulations using streaming flow [77].…”

“…However, if the wall did not have enough strength to hold the compressed DNA, it was pulled by the hydrodynamic drag force back into the vortex. If the flow strength and the wall trapping force are tuned, short DNA strands are trapped in the trap region, the region between two vortices on the stick wall, and long DNA strands rotate freely in the vortices [77].…”

“…They investigated the effect of vortex flow conditions on DNA conformations and positions to show the potential for trapping DNA in vortices [113]. Alfahani et al [77] used the LBM to evaluate the rotating flow field and to include HIs. The LBM followed the same methodology as in the work done by Usta et al [71] [72].…”

“…Microscale rotational flows, or streaming flows, with counter-rotating vortices have been known as another method for trapping particles, or DNA strands [77] [111] [112] [113]. The vortices can be generated by acoustically driven bubbles [111] or by local heating [112].…”