TY - JOUR T1 - A Tandem Cell for Nanopore-based DNA Sequencing with Exonuclease JF - bioRxiv DO - 10.1101/005934 SP - 005934 AU - G. Sampath Y1 - 2014/01/01 UR - http://biorxiv.org/content/early/2014/08/08/005934.abstract N2 - A tandem cell is proposed for DNA sequencing in which an exonuclease enzyme cleaves bases (mononucleotides) from a strand of DNA for identification inside a nanopore. It has two nanopores and three compartments with the structure [cis1, upstream nanopore (UNP), trans1 = cis2, downstream nanopore (DNP), trans2]. The exonuclease is attached to the exit side of UNP in trans1/cis2. A cleaved base cannot regress into cis1 because of the remaining DNA strand in UNP. A profiled electric field over DNP with positive and negative components slows down base translocation through DNP. The proposed structure is modeled with a Fokker-Planck equation and a piecewise solution presented. Results from the model indicate that with probability approaching 1 bases enter DNP in their natural order, are detected without any loss, and do not regress into DNP after progressing into trans2. Sequencing efficiency with a tandem cell would then be determined solely by the level of discrimination among the base types inside DNP. ER -