MSE PhD Final Defense of Margaret Chern

12:00 pm on Monday, April 8, 2019
2:00 pm on Monday, April 8, 2019
8 Saint Mary's Street, Room 339

ABSTRACT: The brightness and photostability of semiconductor quantum dots (QDs) has prompted the exploration of their use in a wide variety of fields. Several examples of QD-based biosensors have been reported but none have actually replaced their preexisting technologies. This work reveals the barriers hindering widespread use of QD based biosensors and examines how QDs can be engineered for improved utility in bioassay designs.

The first portion of this project aims to improve Förster Resonance Energy Transfer (FRET) that use QDs as both the donor and acceptor. FRET-based sensors often use fluorescent dyes (FD) or proteins (FPs), but their photo- and chemical instability can be problematic. Contemporary QD-QD FRET systems suffer from unacceptably high background signal due to direct acceptor excitation. Materials engineering is used to create QD donors that are brighter than their QD acceptors to mitigate this effect. First, CdSe/xCdS/xZnS QDs of increasing shell thickness were synthesized and tested in a QD-fluorescent dye system to elucidate the effect of increased donor size on the performance of a FRET sensor. The optimal donors were medium-sized and 8 times brighter than commercially available QDs while retaining ~60% FRET efficiency. When used in a sensor, changes in sensor brightness were visible by eye. Moving towards QD-QD systems, a pH-based aggregation assay was used to test how QD heterostructures comprised of different semiconductor materials perform as FRET donors or acceptors. The fundamental principles uncovered are used to improve contemporary QD-QD FRET sensing and show that sensors can be designed to use color change as a visible, easy-to-decipher readout.

Color change-based sensor output is further explored in an allosteric transcription factor-based small-molecule sensor that employs QDs as the sole fluorescent label. A highly modular design is presented that achieves a nanomolar concentration visual limit of detection. The ease of use, and fast, instrument-free readout of the sensor shows promise for its development into a fully integrated point-of-care device, endorsing the value of further developing QD-based in vitro biosensors for clinical or commercial translation.

COMMITTEE ADVISOR Professor Allison Dennis, MSE/BME; Professor James Galagan, BME; Professor Tyrone Porter, MSE/ME; Professor Björn Reinhard, MSE/Chemistry; CHAIR: Shyamsunder Erramilli, MSE/BME/Physics