Nanofluidic Device Designs for Selective Biomarker Enrichment Using Electrokinetic Forces

The enrichment and separation of target biomarkers has traditionally been accomplished via chemical depletion methods that are highly selective. However, they are time consuming and labor intensive, enabling no more than a 100 - 1000 fold level of concentration enrichment. Electrokinetic techniques within microfluidic platforms can enable more than 1000 fold enrichment due to the enormous volume reduction. Dielectrophoresis (DEP) is the frequency-selective translation of polarized particles under a spatially non-uniform field and is an extremely powerful electrokinetic technique for concentrating, separating and characterizing many kinds of particles, biological or otherwise, within microfluidic devices. However, DEP trapping forces fall as cube of particle size and are easily disrupted by electrothermal flow due to Joule heating within physiological media. This has limited the application of DEP methods towards biomarker preconcentration, especially since biomarkers are present in extremely dilute samples, with a high quantity of interfering proteins. In this work, we develop the theoretical framework for overcoming this challenge, through the design of micro/nanofluidic devices for coupling DEP with other electrokinetic phenomena towards the pre-concentration, separation and characterization of bio-particles. Specifically we investigate: (1) The coupling of alternating current DEP techniques with direct current ion concentration polarization methods for ultrafast biomarker preconcentration in physiological media at nano-constrictions; (2) The low frequency double layer polarization phenomenon on nanoparticles, including an elucidation of size and media conductivity effects; and (3) development of a methodology for quantifying the DEP force by simultaneous tracking of the translation of single particles within an electrode-less DEP device. This framework is envisioned to enhance the versatility as well as spatial resolution of the DEP technique for selective manipulation of particles within micro/nanofluidic devices.