Realistic Brownian Dynamics simulations of biological molecule separation in nanofluidic devices

Abstract

We present a Brownian Dynamics model of biological molecule separation in periodic nanofilter arrays. The biological molecules are modeled using the WormLike-Chain model with Hydrodynamic Interactions. We focus on short dsDNA molecules; this places the separation process either in the Ogston sieving regime or the transition region between Ogston sieving and entropic trapping. Our simulation results are validated using the experimental results of Fu et al. (Phys Rev Lett 97:018103, 2006); particular attention is paid to the model's ability to quantitatively capture experimental results using realistic values of all physical parameters. Our simulation results showed that molecule mobility is sensitive to the device geometry. Moreover, our model is used for validating the theoretical prediction of Li et al. (Anal Bioanal Chem 394:427-435, 2009) who proposed a separation process featuring an asymmetric device and an electric field of alternating polarity. Good agreement is found between our simulation results and the predictions of the theoretical model of Li et al.

Modeling the Electrophoretic Separation of Short Biological Molecules in Nanofluidic Devices

“…[13]; the focus of that paper was to demonstrate the feasibility of high-field electrophoresis and to highlight the importance of "torque assisted escape'' in the latter limit. More recently, Fayad and Hadjiconstantinou [14] developed a BD formulation based on the WLC [15] model in order to quantitatively model Ogston-regime separation; good agreement with the experimental results of Fu et al [3] was observed.…”

“…In other words, for an efficient model, some degree of coarse-graining is required. For the present application, BD simulations strike a good balance between fidelity and efficiency, and have already been used to model biological molecule separation [11][12][13][14]. Our approach places more emphasis on simplicity and efficiency which are essential in the context of device design and optimization.…”

“…[16], the threedimensional BD model developed below does not make any simplifying assumptions regarding the system geometry, and is significantly more efficient than descriptions of equivalent fidelity, such as numerical solution of the Fokker-Planck equation. In fact, by comparing our simulation results with BD simulations of more complex models (rigid-rod, WLC) [14], as well as the experimental results of Fu et al [3], we show that, provided the molecules modeled are sufficiently short, the partition-coefficient-based BD model Fig. 1 Schematic of one period of the nanofilter array 1 entails virtually no loss in fidelity, while being significantly simpler and at least two-orders of magnitude more efficient compared to rigid-rod or worm-like-chain BD models.…”

Modeling the Interface between Biological and SyntheticComponents in Hybrid Nanosystems

“…To overcome these difficulties, it is common to use particle-based methods like Brownian dynamics [103] to simulate transport in micro-and nanofluidic devices [104], which can be run at a fraction of the cost as MD, but with the loss of atomic-scale precision.…”

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

“…Fayad and Hadjiconstantinou used BD simulation with WLC model considering HI to study the effect of device geometry on the separation process for shorter DNAs. Optimization of the device was also studied [109].…”