Sensitive, Specific Complementary - Strand Optical Detection of Viral RNA

A novel low-cost evanescent wave nucleic acid detector of great speed and dynamic range is proposed. The detector is based around an optical waveguide and a self-compensating interferometer design in contrast to fluorescence based biosensors. The sensor is inherently stable to vibration and temperature variations, and has low power requirements, making it ideal for field use. The chemistries involved in detection are well established and combine dipstick-like ease of use with the sensitivity of complementary-strand hybridization. The design is intended to be compact and lightweight with minimal sample preparation. The extreme precision of the technique requires only small sample volumes or concentrations of analyte even in poorly characterized background environments. Although potentially as general a detection mechanism as PCR, the sensor will be tested for the Phase I on hepatitis sequences due to the abundance of adequate probe oligos and pressing public health needs. The sensor is expected to be easily adaptable to different analytes and inexpensive. The proposed detector addresses excellently the need for rapid pathogen identification and characterization and could be extended to use IgG sensing of viral epitopes, or anti-idiotype sensing for seroconversion, replacing ELISAs for viral detection in serum. The Phase I effort consists of a feasibility experiment to demonstrate the detector's ability to sensitively and specifically detect target hybridization in solution in the presence of nonspecific competitor DNA; sequences will be selected from conserved regions of a viral genome. Work will be extended to detecting the corresponding RNA both synthically produced and in serum to complete the requirements of the Phase I solicitation. The proposed sensor is expected to be of broad and immediate application in viral detection and beyond. The technology is extensible to many other sensing macromolecules (e.g. antibodies) and uses. As examples, the sensor could enhance public and military security measures for defense against chemical or biological terrorism, enable medical technologies to rapidly detect serum-borne toxins or pathogens, and assist basic research.