(192c) Selective Enrichment of Molecular Biomarkers Under Ion Concentration Polarization in Nanochannels Using DC Versus AC Electrokinetics

Selective and rapid enrichment of biomarkers can have transformative impacts within various biosensing paradigms. Affinity methods based on antibody depletion can cause enrichment levels of no more than two to three orders of magnitude. Since typical biomarkers are at million-fold levels lower than interfering proteins or circulating antibodiers, there is a need for complementary enrichment modalities. The current state of the art uses ion concentration polarization in nanochannels to enhance localized fields under DC electrokinetics. Specifically, localized ion depletion at the anodic interface of the microchannel to perm-selective nanochannel is used to enhance electric fields and the resulting biomarker electromigration is balanced against electro-osmosis in the microchannel to cause biomarker enrichment. However, selective enrichment of biomarkers with like-charges, such as prostate specific antigen versus interfering circulating antibodies is not possible and the enrichment levels fall off within physiological media of high conductivity, due to a reduction in ion concentration polarization and electro-osmosis. Herein, we present a comparison of this DC electrokinetic method versus an analogous AC electrokinetic method that also uses a DC offset to locally modulate field profiles by ion concentration polarization. Specifically, by utilizing AC fields at a critical frequency to selectively translate the biomarker of interest by negative dielectrophoresis and a critical offset DC field to create an ion accumulation region proximal to ion depletion along the cathodic interface of the perm-selective region inside a nanoslit, this method seeks to enhance the spatial extent for enabling biomarker enrichment. While enrichment under DC electrokinetics relies solely on ion depletion to enhance fields, the AC electrokinetic mechanism utilizes ion depletion as well as ion accumulation regions to enhance the field and its gradient. Hence, biomarker enrichment under AC electrokinetics continues to be substantial within physiological media, in spite of the lower perm-selectivity. In this manner, by selectively enriching prostate specific antigen versus anti-mouse immunoglobulin antibodies, we demonstrate the elimination of false positives to the immunoassay.