SBIR Phase I: Pathogen Interception: A new method for finding and identifying genetic sequences

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The broader impact of this Small Business Innovation Research (SBIR) Phase I project will be the ability to quickly and inexpensively determine the presence and genetic sequence of a wide variety of pathogenic organisms. Most importantly, this technology could be implemented without prior assumptions as to which organisms are expected. Sequencing will be accomplished by direct electrical identification of the building blocks, the bases, of the genomic sequence. The potential societal impact of this technology is to provide a method to screen individuals quickly (under a minute) for the presence of infections. Screening at ports of entry and in appropriate community settings will minimize disease transmission and allow for the quick identification and treatment of any infected individuals at US borders. In addition, beyond this immediate application, the technology may also enhance scientific understanding of normal genetic sequences in any organism. If its anticipated speed, high accuracy, and low cost are realized, this technology may find applications in human in vitro diagnostics and human genome sequencing. The studies in this Phase I project will lead to a proof-of-concept demonstration for an automated, commercial instrument.The project seeks to determine the identity and order of the genetic building blocks, the nucleotide bases, comprising any genomic sequences present in a sample solution. This sequencing will be done by examining the ability of each base in the sequence to modify a tunneling current as it is passed by electrophoresis across two very closely spaced tunneling electrodes. Tunneling is a well-known quantum mechanical effect, and it is quite sensitive to the electrical configuration of the object (here a given specific nucleotide base) present between its electrodes. Experiments with this technology to date have been unsuccessful because genetic sequences have not been able to be moved slowly enough across the tunneling electrodes for their bases to be distinguished. The studies here will overcome this problem by modifications of the geometry and solution conditions of the electrophoresis and possibly with improved methods of tunneling current detection. The data obtained through the application of this technology is expected to enhance the current understanding of nucleotide base chemistry. The solution may permit the detection of nucleotide base modifications of potential biological and medical importance.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.