Mixed-domain simulation of electrophoretic DNA separation for CMOS IC design

Abstract

Electrophoretic separation is a key technology for DNA sequencing, environmental pathogen detection and identification, disease diagnostics, and proteomics. However, current electrophoresis systems are limited to laboratory benchtop applications due to cost and size. Even current chipbased electrophoresis systems require high voltages and are several centimeters in length, effectively preventing wide pointof-care and field use. A small (less than 1 cm), mass producible, low voltage (less than 5 V) electrophoretic system could move this powerful technology off the benchtop, out of the lab, and into wide use. A CMOS system on a chip has been proposed that would produce dynamic electric fields to dramatically reduce the operating voltages required for electrophoretic separation, and the fine resolution available in CMOS technology can be used to shorten the column lengths necessary for successful separation. Traditional circuit simulation is not suitable for a system that is characterized by electromagnetic fields and fluid behavior.A specialized mixed-domain simulation has been developed to determine the effectiveness of this system for DNA separation. Terminal restriction fragment length polymorphism (T-RFLP) analysis has been shown to be a particularly useful method of DNA analysis for pathogen identification, and its use as a feasible method on the electrophoresis system is investigated.

Low electric field DNA separation and in‐channel amperometric detection by microchip capillary electrophoresis

“…To‐date various sensing methods have been investigated and new measuring circuits proposed. Lin used a moving field strategy to reduce the separation voltage [15], whereas Wake and Brooke [16] used a similar technique for the same purpose. Although very low separation voltages have been achieved, these techniques are yet to be realised because of the complexity in electronics.…”