The overuse of antibiotics has led to soaring rates of antibiotic resistance in the U.S. More antibiotic prescriptions are written for upper respiratory infections, such as respiratory syncytial virus (RSV), than for any other indication. Physicians self-report that these prescriptions would be inappropriate for a viral diagnosis. Rapid diagnostic tests would give physicians the information needed to avoid inappropriate antibiotic use. Because of their unique specificity and plasticity, antibody-based strategies continue to be a key component of many virus detection platforms. However, a major stumbling block of high-sensitivity antibody-based detection technologies is the innate presence of non-specific interactions between antibodies and non-targets. This application describes a method to combine DNA reporter tags and logical operations among DNA-antibody tags to develop a new paradigm in DNA tag-based virus detection. In the proposed approach, instead of specifying unique, but arbitrarily chosen DNA sequences as DNA-antibody tags, the DNA sequences are purposely designed to facilitate logical operations among tags. In Aim 1 these "DNA logic tags" will be designed, tested, and co-coupled with antibodies to gold nanoparticle surfaces. It is hypothesized that this logic tag approach will permit control of non-specific antibody interactions using a logical NOT operation (Aim 2), and a means to independently fine-tune detection sensitivity and specificity using logical OR and operations among tags (Aim 3). These hypotheses will be evaluated by measurements of the effect of the logical operations on the sensitivity and specificity of an RSV detection assay performed in an increasingly complex biological environment. Highly sensitive and specific diagnostic tools, such as proposed here, will become increasingly important in point-of-care diagnostics to rapidly identify pathogens and help guide the choice of appropriate therapeutic treatment. PUBLIC HEALTH RELEVANCE: More antibiotic prescriptions are written for upper respiratory infections (an estimated 100 million prescriptions a year) than for any other indication, and doctors self-report that these prescriptions would be inappropriate if a viral diagnosis was available. Rapid, simple and accurate diagnostic tests for early detection of respiratory virus infections are sorely needed. The goal of this project is to evaluate a new viral detection technology for the medically important exemplar, respiratory syncytial virus.