Applications of Digital Microfluidics for the Extraction and Analysis of Small Molecules from Solid Samples

Digital microfluidics (DMF) has emerged as a valuable technology that may be useful in the goal of realizing true lab-on-a-chip (LOC) or total micro analysis systems (µTAS). DMF is a relatively new microscale liquid-handling technique in which droplets of fluid are manipulated on a flat, two-dimensional array of electrodes coated with a hydrophobic insulator. Droplet movement is driven by the application of electric potentials to successive electrodes, enabling a droplet to be dispensed from a reservoir, merged, mixed and split. One of the strengths of DMF when compared to channel microfluidics is the ease with which DMF can process solid samples, and incorporate solid materials into sample preparation work-flows without the risk of clogging.This thesis describes the exploration of digital microfluidics as a tool for working with solid samples and matrices. Chapter two describes the first method useful for analyzing multiple hormones in dried blood. This method broadens the scope and breadth of information available from the analysis of dried blood spotted directly onto device. Chapter three describes the first method for applying digital microfluidics towards the analysis of pharmaceuticals from blood spotted onto filter paper - dried blood spots (DBS). The DMF method is compared to the traditional macroscale method employed by collaborators at GlaxoSmithKline. Chapter four describes the first combination of DMF and miniature mass spectrometry (MS). This newly developed, automated, multiplexed, and portable platform was designed for the extraction of illicit drugs from dried urine, and is designed to replace the traditional two-tiered urine analysis system with a one-tiered total analysis system. Chapter five describes a new method for on-chip solvent optimization using a design of experiment. Using this system, C18-coated magnetic beads were incorporated onto device, enabling the first instance of fractionation on a DMF device. Finally, chapter six summarizes the principles and concepts derived from this work, and concludes with a look forward to future applications of digital microfluidics as a tool to handle solid samples and matrices.Ph.D