Terahertz Time Domain Spectroscopy of Conformational Dynamics of Sensor Proteins: Basic Research and Pathogen Sensor Development

摘要

We report on the research funded in part by this ARO grant towards developing an all-optical terahertz biosensor. This program is motivated by the need for fast and adaptable biosensors that do not require probe labeling. Our sensors are based on an intrinsic change in the probe molecule's physical characteristics upon target binding, namely the THz absorption. The proposed sensor consists of a compact THz spectroscopy system based on electro-optic imaging of a sample matrix. The sample matrix made from xerogel would have defined regions of probe molecules as well as regions for referencing. This sample substrate would allow for both high THz optical density and easy access of airborne targets to bind to the embedded probe molecules. The stated goals in the original proposal for this first funding period were as follows: (1) spectral benchmarking of probes: free and complexed focusing on benign targets to establish sample protocols, (2) initial xerogel array development and(3) initial construction of EO imaging system. All three of these initial goals have been achieved. We will discuss spectral benchmarking for lysozymelN- acetylglucosamine, anti-lysozymellysozyme, deoxy cytochrome doxygen and deoxy myoglobinloxygen binding. We will also present our xerogel characterization as a function of hydration. In all cases we see a significant change in the THz absorbance with ligand binding, supporting the suggested strategy of using THz absorbance as a labeless method of biodetection. In the coming year we will attempt to print a xerogel with different proteins and then expose the gel to aerosols of target molecules to determine binding efficiency for this sample prep. We will attempt to detect the binding both with standard THz spectroscopy as well as using THz imaging.