Microfluidic multiple cross-correlated Coulter counter for improved particle size analysis

Coulter counters (a.k.a. resistive pulse sensors)were widely used to measure the size of biological cells and colloidal particles. One of the important parameters of Coulter counters is its size discriminative capability. This work reports a multiple pore-based microfluidic Coulter counter for improved size differentiation in a mixed sample. When a single particle translocated across an array of sensing pores, multiple time-related resistive pulse signals were generated. Due to the time correlation of these resistive pulse signals, we found a multiple cross-correlation analysis (MCCA)could enhance the sizing signal-to-noise (SNR)ratio by a factor of n^1/2, where n is the pore numbers in series. This proof-of-concept is experimentally validated with polystyrene beads as well as human red blood cells. We anticipate this method would be highly beneficial for applications where improved size differentiation is required.