DNA transport by a micromachined Brownian ratchet device

Abstract

We have micromachined a silicon-chip device that transports DNA with a Brownian ratchet that rectifies the Brownian motion of microscopic particles. Transport properties for a DNA 50-mer agree with theoretical predictions, and the DNA diffusion constant agrees with previous experiments. This type of micromachine could provide a generic pump or separation component for DNA or other charged species as part of a microscale lab-on-a-chip. A device with reduced feature size could produce a size-based separation of DNA molecules, with applications including the detection of single-nucleotide polymorphisms. The Human Genome Project aims to provide the complete sequence of the 3 billion base pairs of the human genome. While the dominant method for analyzing DNA fragments remains gel electrophoresis, new technologies that have the potential to increase the rate and decrease the cost of DNA sequencing and analysis, such as mass spectrometry and hybridization arrays, are critical to the project's success (1).Here we describe a method of DNA transport and separation based on a Brownian ratchet. As described originally by Smoluchowski (2) and noted by Feynman (3), a Brownian particle can undergo net transport on a potential energy surface that is externally driven to fluctuate between several distinct states. Brownian ratchets have attracted theoretical attention (4-12) because of their description of molecular motors (13-15) and their similarity with phenomena termed stochastic resonance and resonance activation (16,17).Brownian ratchets have been demonstrated to transport micrometer-to millimeter-sized particles in experiments with ratchets generated by dielectrophoresis (18), optical tweezers (19), and electrocapillary forces (20,21). Other devices based on entropic ratchets (22) or physical barriers (23, 24) have been proposed as well. More recently, a geometrical sieve device has been used to separate phospholipids (25).Despite these successes, the Brownian ratchet mechanism has not before proved capable of transporting DNA fragments in the size ranges applicable to DNA sequencing (Ͻ1000 nt) because the interactions used to establish the ratchet potential were too weak. In contrast to previous devices using polarization interactions to generate ratchets (18,19), the device that we have fabricated uses charge-charge interactions to generate the ratchet potential. As seen below, the charge-charge interactions have sufficient strength to establish ratchets that can trap small DNA fragments.The ratchet-like wells that trap DNA are generated by charging a series of patterned electrodes. When the electrodes are discharged, the traps vanish and the molecules undergo Brownian motion. Next the potential is reapplied, and the particles again collect in the traps. A spatial asymmetry in the shape of each ratchet-shaped well rectifies the Brownian motion and produces net transport as the on-off cycle is repeated. Each molecule's transport rate depends on its diffusion constant, allowing the possibility of size-based separations. We...

Theory of DNA electrophoresis (∼ 1999 –2002 ½)

“…Their system induces directed motion of latex beads (1-6 mm in diameter) using an oscillating electric field (of zero mean value) in a microfabricated channel with an asymmetrically modulated diameter. Another prime example of a successful Brownian rectifier is the one built by Bader and co-workers [49][50][51] for DNA oligomer separation in free solution. Their device consists of interdigitated electrodes which produce a simple asymmetric sawtooth potential (see Fig.…”

Observation of Flux Reversal in a Symmetric Optical Thermal Ratchet

“…Rather, this is an instance of a so-called drift ratchet [20]. Other pioneering implementations of classical force-free thermal ratchets also were based on asymmetric potentials, but did not exhibit flux reversal [21,22,23,24,25]. Figure 1 shows the principle upon which the three-state optical thermal ratchet operates.…”

Stabilization of ratchet dynamics by weak periodic signals

“…The damping and the asymmetry of the potential are crucial ingredients for this conversion, both in the multiplicative [1, 3,4] and in the additive [4,5,6,7] case. This phenomenon arises in a variety of different systems and has been used to design new experimental devices both for physical and biological applications [8,9,10,11,12,13,14]. Moreover, the ratchet effect is presently considered as a possible mechanisms by which molecular motors (e.g.…”