Molecular and Nanoscale Strategies for Enhanced Biosensing

As personalized medicine advances, the need continues to grow for new sensors in applications ranging from clinical diagnostics to therapeutic development. Biosensors are powerful tools and their evolution will play an important role in healthcare by enabling the detection of specific analytes that are clinically significant. The central aim of this thesis is to formulate new sensing strategies to detect clinically relevant biomolecules in a sensitive and specific manner. Many target analytes are present at extremely low concentrations while remaining relevant. The utility of a biosensor is limited by its sensitivity; but also, as we investigate herein, its ability to maintain its function in a heterogeneous environment. Here, we develop a novel sensing method for low concentration analysis of soluble signaling factors by coupling DNA hybridization engineering and antibody-capturing chemistry with an electrochemical-based reporting method. This technique – when combined with a chip-based approach – allows for both sensitive and rapid detection. Through the use of nanostructured electrodes, we showcase our technologies in applications that include protein quantification and low-level light detection. We design a device that analyzes multiple small signaling proteins in stem cell cultures with 10 pg·mL-1 sensitivity and validate our results by comparing them to the gold standard enzyme-linked immunosorbent assay, with more suitable integration capability and in-line monitoring along with smaller sample sizes and decreased process times. This platform is improved by further developing a reusable, multiplexed one-step assay and sensor, simplifying and speeding up the steps required to obtain readout. Finally, we report on nanogap-separated fractal electrodes as a method for the formation of nanoscale features, exhibited by the fabrication of quantum dot photodetectors with nearly a one hundredfold improvement in performance over that of conventional devices. Overall, these strategies present important steps toward the development of more sensitive and faster sensors. By demonstrating low concentration analysis in complex environments and unprecedented performance with novel methods, we forge a pathway to more cost-effective and powerful sensing.Ph.D