Fluidic Diodes in Nano- and Microscale Pores to Detect Drug Aggregation

Abstract

We present a novel method of producing ion current rectification (ICR) in nano- and micro- scale pores that does not require electrical double layer overlap within a pore. ICR in nanopores has typically been constrained in two ways: i) at least one dimension or component of the channel must be on the order of the Debye screening length and ii) charge asymmetry must be induced within the pore. Asymmetric channel geometries, modified surface charges, and asymmetric bulk ion concentrations are commonly applied to produce the necessary charge asymmetry. In the method presented here, ICR is dependent on electroosmotic flow (EOF) to position two solutions of different conductance within a pore. Substrates containing pores with diameters of 10 nm, 30 nm, and 500 nm were used to separate the two different solutions. We have achieved rectification factors ranging from 2-15, as a function of solution properties, in conical and cylindrical pores with diameters much larger than the Debye screening length. Thus, ICR can be achieved at higher ionic strengths (here up to 300 mM), in pores with large diameters (here up to 3 μm), and in pores without patterned surface charges. We also present a phenomenon unique to the two-solution system that we introduce here. Dissolving a drug in one solution, which contains 75%, DMSO, and then moving the molecules through the pore into a purely aqueous solution leads to detectable aggregation of the drug in the pore. The aggregate typically proceeds to the point of blocking the pore (>85% reduction in current) and subsequently ejects from the pore. We have investigated the aggregation and subsequent clearance of the aggregate from the pore and propose a mechanism for the cyclic process.