The investigator's aim is to develop a miniaturized Coulter counter through which a single chain of ssDNA is drawn. As different bases pass through the narrow portion of the channel, the current leaking through the DNA and the residence time will be different for the different bases. They propose to use ssDNAs denatured by high temperatures and non-aqueous solvents. Fluid flow and/or electrical gradient in the pipette will straighten the DNA prior to reading. Various schemes have been proposed to resolve anticipated problems in terms of on-line recording conditions, DNA alignment conditions, chemical modification of pipette surface and/or the polymer, and the use of latex beads in order achieve the required one-base resolution and the signal differences among the four DNA bases. The method could be extended to RNA and protein sequencing.
