Resistive-pulse sensing is a label-free, nondestructive, single particle analysis technique that provides information about the size and surface charge of nanoscale particles. Resistive-pulse sensing requires a supporting electrolyte to act as a charge carrier that is displaced as a particle traverses a nanoscale pore, resulting in a change in resistance and corresponding current pulse. The pulse amplitude is proportional to the concentration of the electrolyte, and as the electrolyte concentration is increased, the signal-to-noise ratio improves. Consequently, the concentration of the electrolyte in which the sample resides often limits the types of samples that can be analyzed by resistive-pulse sensing. Specifically, samples dissolved in low concentrations of electrolyte are not easily analyzed with traditional devices because of the low signal-to-noise ratio. We have designed a device with a nanoscale mixing tee integrated adjacent to the nanopore sensing region. One channel contains the sample, the other channel has a more concentrated solution of NaCl (&gt;1 M), and the two solutions are mixed just prior to the detection region. The increase in electrolyte concentration leads to a substantial increase in the signal-to-noise ratio. This new design effectively allows samples dissolved in low electrolyte concentrations to be easily investigated with resistive-pulse sensing.

Resistive-pulse sensing on in-plane nanofluidic devices with integrated mixing tee and pores for improved detection limits

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