The ability to understand and to manipulate protein-protein interactions will contribute to improvements in biological imaging and methods for drug discovery and delivery. One crucial component of protein interactions is the binding site. The strength of the interaction determines the utility of the two proteins, which could be an antibody-antigen or an enzyme-substrate pair. Different methods have been developed to characterize this interaction, yet these techniques require either high protein pair concentrations or imaging of the interaction. High concentrations often cause blurring in the final data. Therefore, to accurately determine the interaction between two proteins, it is important to perform both types of measurements. The primary focus of this project is to develop and to demonstrate an optical sensor capable of characterizing antibody-antigen binding at the single molecule level without relying on images. This instrument is based on an optical sensor that relies on resonance, somewhat like an acoustic tuning fork. The optical sensor is capable of single molecule detection, because as molecules bind to the sensor, the sensor?s resonant frequency changes, resulting in a fast response time (100ns) and improved sensitivity. This technique will enable new types of measurements that will have immediate impact on the fields of cell biology and biochemistry, with longer-term benefits to systems biology. Training future scientists and engineers at all age levels is an integral component of this project. In addition to the involvement of a graduate student and a post-doctorate scholar, several undergraduate researchers whose stipends are provided through USC?s Undergraduate Research Fund will be involved in different aspects of this project. They will have the opportunity to learn state-of-the-art instrumentation and fabrication methods in USC?s Class 10 cleanroom and electron microscopy center. Results will be presented at professional conferences and the equipment will be demonstrated to middle school and high school visitors to the laboratory.

Project Report

This highly interdisciplinary program has drawn together researchers from different fields to advance technologies which can enable diagnostics and biophysics investigations. Specifically, during the course of this research, novel methods for attaching a wide range of biomolecules to optical device surfaces have been developed. To accomplish this task, several critical hurdles regarding attachment density, device integrity and biomolecule stability were addressed. Additionally, a new suite of thin film glasses have been designed and synthesized, and they have formed the foundation of a new class of microlasers. During this portion of the research, the researchers synthesized and characterized the thin films as well as fabricated and measured the microlaser device performance. Many of these devices exhibited record performance characteristics. Finally, by combining the advances in surface chemistry and in device physics, new methods of performing highly sensitive biodetection experiments have been demonstrated. Some representative examples include the detection of ssDNA hybridization at room temperature, the measurement of protein binding kinetics in real-time, and the self-assembly of lipid bilayers. Additionally, in a complementary effort, 3D multiphysics finite element method simulations were performed to thoroughly understand the transport of proteins to the surface of the sensing elements. The research team which accomplished this work spanned from high school students through post-doctoral scholars, and included researchers from both the fundamental sciences (biology and chemistry) as well as different areas in engineering (e.g. EE, CHE, Mat Sci, BME). Over half of the students supported by this award were from under-represented groups in engineering (minority or female), and over half of the undergraduates are now pursuing PhDs.

National Science Foundation (NSF)
Division of Biological Infrastructure (DBI)
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Program Officer
Joyce Fernandes
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University of Southern California
Los Angeles
United States
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