Despite the continuous advancement of analytical techniques, low analyte concentration, limited sample volume, and complexity of matrices still present major challenges in clinical, bioanalytical, and environmental sample preparation and separation. The need for improved limits of detection (LOD), specificity, and decreased analysis time are the main challenges that drive the development of new technologies.

For the past few decades, microfluidic platforms have enabled the development of high impact technologies, such as wearable devices for diabetes and for chronic heart disease management. Microfluidic or lab-on-chip devices can be integrated with fluidic structures, electrodes, and chemically-modified surfaces to confer several distinct advantages including efficient handling of small volumes, rapid analysis, and access to surface-driven physical phenomena such as electrokinetics. Electrokinetic forces are ideal for manipulating transport of charged species, e.g., nucleic acids, proteins, and cells, which are often used as important biomarkers for disease diagnosis.

Ion concentration polarization (ICP) is an electrokinetic phenomenon that occurs due to a simultaneous enrichment and depletion of ions at opposing ends of an ion permselective structure, ether a membrane (ICP) or an electrode (faradaic ICP, fICP), when an electrical field is applied across it. A locally enhanced electric field forms within the ion depleted region due to low ionic conductivity. The sharp spatial variation in background electrolyte concentration at the boundary of this region results in a steep electric gradient that has been employed for enrichment and separation of charged species for analysis, mainly in simple media (buffer solutions).

Despite recent advancements in ICP and fICP, a few challenges remain. For example, focusing of neutral (uncharged) species, application of ICP in highly conductive or complex media (e.g., biological fluids), development of strategies to decrease fluidic instability in the high electric field zone, improvement of volumetric throughput, and integration with downstream analysis are all active areas of research.

The objectives of this dissertation address the current limitations of ICP by developing 1) ICP-based methods for chemical separations in biological fluids, 2) methods for the separation and enrichment of neutral (uncharged) species, 3) fundamental strategies to increase the stability of ICP, thereby allowing for increased device throughput, and 4) a platform that can be integrated with downstream analysis for low abundance analyte detection in POC settings. The outcome of this work will be broader application of ICP for the analysis of a wide range of biological species, especially for point-of-need applications.