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Digital microfluidics (DMF) has recently emerged as a popular technology for a wide range of applications. In DMF, nL-mL droplets containing samples and reagents are controlled(i.e., moved, merged, mixed, and dispensed from reservoirs) by applying a series of electrical potentials to an array of electrodes coated with a hydrophobic insulator. DMF is distinct from microchannel-based fluidics as it allows for precise control over multiple reagent phases (liquid and solid) in heterogeneous systems with no need for complex networks of microvalves. In this thesis, digital microfluidics has been applied to address key challenges in the fields of chemistry, biology and medicine. For applications in chemistry, the first two-plate digital microfluidic platform for synchronized chemical synthesis is reported. The new method, which was applied to synthesizing peptide macrocycles, is fast and amenable to automation, and is convenient for parallel scale fluid handling in a straightforward manner. For applications in biology, I present the first DMF-based method for extraction of proteins (via precipitation) in serum and cell lysate. The performance of the new method was comparable to that of conventional techniques, with the advantages of automation and reduced analysis time. The results suggest great potential for digital microfluidics for proteomic biomarker discovery. Furthermore, I integrated DMF with microchannels for in-line biological sample processing and separations. Finally, for applications in medicine, I developed the first microfluidic method for sample clean-up and extraction of estrogen from one-microliter droplets of breast tissue homogenates, blood, and serum. The new method is fast and automated, and features >1000x reduction in sample use relative to conventional techniques. This method has significant potential for applications in endocrinology and breast cancer risk reduction. In addition, I describe a new microfluidic system incorporating a digital microfluidic platform for on-chip blood spotting and processing, and a microchannel emitter for direct analysis by mass spectrometry. The new method is fast, robust, precise, and is capable of quantifying analytes associated with common congenital disorders such as homocystinuria, phenylketonuria, and tyrosinemia.

Digital microfluidics (DMF) has recently emerged as a popular technology for a wide range of applications. In DMF, nL-mL droplets containing samples and reagents are controlled(i.e., moved, merged, mixed, and dispensed from reservoirs) by applying a series of electrical potentials to an array of electrodes coated with a hydrophobic insulator. DMF is distinct from microchannel-based fluidics as it allows for precise control over multiple reagent phases (liquid and solid) in heterogeneous systems with no need for complex networks of microvalves. In this thesis, digital microfluidics has been applied to address key challenges in the fields of chemistry, biology and medicine. For applications in chemistry, the first two-plate digital microfluidic platform for synchronized chemical synthesis is reported. The new method, which was applied to synthesizing peptide macrocycles, is fast and amenable to automation, and is convenient for parallel scale fluid handling in a straightforward manner. For applications in biology, I present the first DMF-based method for extraction of proteins (via precipitation) in serum and cell lysate. The performance of the new method was comparable to that of conventional techniques, with the advantages of automation and reduced analysis time. The results suggest great potential for digital microfluidics for proteomic biomarker discovery. Furthermore, I integrated DMF with microchannels for in-line biological sample processing and separations. Finally, for applications in medicine, I developed the first microfluidic method for sample clean-up and extraction of estrogen from one-microliter droplets of breast tissue homogenates, blood, and serum. The new method is fast and automated, and features >1000x reduction in sample use relative to conventional techniques. This method has significant potential for applications in endocrinology and breast cancer risk reduction. In addition, I describe a new microfluidic system incorporating a digital microfluidic platform for on-chip blood spotting and processing, and a microchannel emitter for direct analysis by mass spectrometry. The new method is fast, robust, precise, and is capable of quantifying analytes associated with common congenital disorders such as homocystinuria, phenylketonuria, and tyrosinemia.