Optimizing a simple biosensor for theophylline

BIOL 142

Brian D. McCarthy, bmccarthy-07@sandiego.edu, Brenda S. DeLa Cruz, and Thomas P. Shields, tshields@sandiego.edu. Department of Chemistry & Biochemistry, University of San Diego, 5998 Alcala Park, San Diego, CA 92110
A simple fluorescent biosensor that detects clinically relevant theophylline concentrations and shows a high level of selectivity for theophylline over caffeine has been developed. Hybridization of well-characterized theophylline binding RNA aptamer to short complementary fluorescein-labeled DNA strands (FL-DNA, 10 - 20 nucleotides long) yields an FL-DNA:RNA hybrid that is sensitive to theophylline. The biosensor retains the selectivity of the RNA aptamer and is sensitive to clinically relevant concentrations of theophylline (e.g. 0 – 50 µM). Recently, dual labeled DNA strands were substituted for the fluorescein-labeled DNA strand to increase the dynamic range of this simple biosensor. In the current study, the length of the DNA probe was optimized in order to increase the dynamic range of the biosensor without sacrificing sensitivity or selectivity. Both circular dichroism spectroscopy, fluorescence spectroscopy and melting temperature analyses were used to study DNA:DNA and DNA:RNA duplexes that are relevant to the hybridization biosensor.