(365i) Nanofluidic Devices for DNA and Protein Pre-Concentration In High-Conductivity Media

Nanofluidic device design criterion for dielectrophoresis pre-concentration of functional ss-DNA and protein biomarker targets within media of high ionic strength, for eventual application towards clinical diagnostic systems of enhanced speed, sensitivity and selectivity are addressed in this presentation. The challenge of sensing rare numbers of biomarker target molecules against a background of high concentration of other matrix proteins can be addressed through selective biomarker pre-concentration. Dielectrophoresis (DEP) enables highly selective trapping of bio-particles based on the characteristic frequency response of the dielectric permittivity of the bio-particle versus that of the medium, and it has been extensively applied towards sorting of somewhat similar sized biological cells with differing dielectric frequency response. However, dielectrophoresis trapping of sub-50 nm bio-particles in high conductivity media is a challenge since temperature gradients due to localized Joule heating can lead to dissipative electrothermal flow. In this presentation, through device-level model simulations and experimental validation we aim to elucidate the criteria for designing devices for pre-concentration of sub-50 nm sized ss-DNA and ~5 nm scale proteins, so that DEP trapping is not hindered by dissipative electrothermal flow, while the sampled fluid volume is enhanced. DEP forces scale as the product of the field and its gradient (E.dE/dx or Del(E²), while electrothermal forces scale as the second exponential power of electric field (σE²), with no dependence on the electric field gradient. Hence, we seek to design constriction-based DEP devices that enhance electric field gradients over the net electric field intensity, to enhance DEP trapping forces over dissipative electrothemal forces. Through varying bio-particle size, media conductivity and constriction scaling factors, in positive and negative DEP modes, we present a scaling analysis for the balance of DEP versus electrothermal forces for nanofluidic designs that enable ss-DNA and protein pre-concentration. Finally, the design is applied towards the continuous monitoring of the enhancement of target binding kinetics as a function of degree of pre-concentration.