Optimization of ELFSE DNA sequencing with EOF counterflow and microfluidics.

We present a nonlinear optimization study of different implementations of the DNA electrophoretic method "End-labeled Free-solution Electrophoresis" in commercial capillary electrophoresis systems and microfluidics to improve the time required for readout. Here, the effect of electro-osmotic counterflows and snap-shot detection are considered to allow for detection of peaks soon after they are electorphoretically resolved. Using drag tags available in micelle form, we identify a design capable of sequencing 600 bases in 2.8 min.

Modeling and Global Optimization of DNA separation.

We develop a non-convex non-linear programming problem that determines the minimum run time to resolve different lengths of DNA using a gel-free micelle end-labeled free solution electrophoresis separation method. Our optimization framework allows for efficient determination of the utility of different DNA separation platforms and enables the identification of the optimal operating conditions for these DNA separation devices. The non-linear programming problem requires a model for signal spacing and signal width, which is known for many DNA separation methods. As a case study, we show how our approach is used to determine the optimal run conditions for micelle end-labeled free-solution electrophoresis and examine the trade-offs between a single capillary system and a parallel capillary system. Parallel capillaries are shown to only be beneficial for DNA lengths above 230 bases using a polydisperse micelle end-label otherwise single capillaries produce faster separations.