UCLA

With the development of technology to characterize and to manipulate objects at the nanoscale, our understanding of the world at the molecular level has opened the way for techniques to create functional surfaces that can interact with other small objects such as cells and biological molecules. The focus of the work embodied in this thesis is twofold: firstly, several devices with the intention of introducing genetic cargo into cells and secondly, aptamer field-effect biosensors to detect small molecules such as neurotransmitters. Both applications utilize aspects of chemical functionalization of surfaces at the nanoscale to imbue the desired properties of the devices.Towards the goal of enhancing the throughput of gene therapies for genetic disorders, microfluidic devices assembled on piezoelectric substrates were created. We achieved cellular transfection on a model cell line through optimizing the acoustofluidic manipulation of cells. A parallel approach with the same goal was to functionalize lipid bilayers to the walls of microfluidic cell-squeezing devices, another method of transfection. We demonstrated that lipid bilayers reduced the fouling of proteins and cellular debris in the flow channel which impacts device lifetime. For small-molecule detection, an area of great interest is the study of neurotransmitters in vivo. In the developments of our biosensors, aptamers, or single stranded sequences of DNA, are functionalized to the surface of a semiconductor transistor using a series of organic chemical linkers. These sequences are designed to selectively bind to a target molecule of interest such as serotonin. The sensors monitor the electrical current between electrodes across the semiconductor, which is altered by the chemical binding. In my work, I aimed to enhance the time response for real-time monitoring by incorporating the sensors in a fluidic system to investigate aptamer binding kinetics. Custom electronics to measure the transistors were also built, with an emphasis on multiplexing and portability.