Improving Disease Diagnostics using Microfluidics

Microfluidic techniques have the potential to greatly improve global healthcare through the development of devices for disease diagnosis and characterization. This thesis explores a number of elements relating to the use of microfluidics to develop devices for biosensing. A droplet microfluidic device was used to perform phenotypic profiling of single and multi-surface biomarkers on live individual cancer cells. The device demonstrated the ability to identify subpopulations of cancer cells that expressed differential expression levels of biomarkers from the main population. This device also detected the combined presence of two biomarkers of interest on cell surfaces. Next, an electrochemical assay that can interface with synthetic gene circuits to detect nucleic acid targets was developed. The capabilities of this system were demonstrated through the multiplexed detection of mobilized colistin resistance genes that impart antibiotic resistance to colistin in a microfluidic channel. A readout system was also created to convert electrochemical currents from the detection of a target into a visual colorimetric readout. Using this system, clinically relevant concentrations of nucleic acid targets can be detected in 10 min. Additionally, an integrated and simple-to-use microfluidic device was designed to translate a laboratory assay for detecting viral nucleic acids into a format suitable for point-of-care diagnostics. This device demonstrated the ability to detect viral nucleic acids from blood in 30 min using passive fluidic actuation methods with minimal sample handling from the user. Together these studies explore the use of microfluidic techniques to provide improvements for disease monitoring.Ph.D