UC San Diego
Nanoscale optoentropic transduction mechanisms
- Author(s): Sullivan, Benjamin David
- et al.
Detection of rare, single base pair mutations of genomic DNA within complex biological samples requires exceedingly specific detection methods. All known molecular amplification protocols have been shown to be compromised by the thermodynamics of hybridization. The current dissertation explores bioelectromechanical analogues of information theory in an attempt to create a noise- tolerant detector. Specifically, modulation of intermolecular DNA fluorescent resonant energy transfer (FRET) systems are used to transmit repetitive codes across a noisy channel. By exploring the optical transduction of the free energy of hybridization into a time-varying signal, we gather direct evidence for complementary, mismatched, and nonspecific binding of singly detectable nanoparticle constructs. Electrophoretic actuation was used to drive molecular transduction systems. Responses were observed using a custom built epi- fluorescent microscope through continuous and co-modulated detectors. FRET dynamics of two subsequences of the p53 gene revealed sequence and mismatch-dependent behavior. Theoretical models of modulation suggested that substantial improvements in specificity are achieved through eigenvector decompositions of modulated FRET signals