An Analytical Differential Resistance Pulse System Relying on a Time Shift Signal Analysis-Applications in Coulter Counting.

Improving the sensitivity and ultimately the range of particle sizes that can be detected with a single pore extends the versatility of the Coulter counting technique. Here, to enable a pore to have greater sensitivity, we have developed and tested a novel differential resistive pulse sensing (DiS) system for sizing particles. To do this, the response was generated through a time shift approach utilizing a "self-servoing regime" to enable the final signal to operate with a zero background in the absence of particle translocation. The detection and characterization of a series of polystyrene particles, forced to translocate through a cylindrical glass microchannel (GMC) by a suitable static pressure difference using this approach, is demonstrated. An analytical response, which scales with the size of the particles employed, was verified. Parasitic capacitive effects are discussed; however, translocations on the millisecond time scale can be detected with high sensitivity and accuracy using the approach described.