Ultrasensitive, Ultradense Nanoelectronic Biosensing with Nanoparticle Probes

摘要

A robust and effective model for determining the presence or absence of an analyte in a DPN-assembled gold nanoparticle/DNA conjugate structure in the limit of single molecule binding was developed. The capacitance picture of semi-classical mesoscopic transport provides both greater sensitivity and greater reproducibility than focusing on the charge transport within the DNA. Effectively, the capacitance model works well in the coulomb blockade limit that is relevant for such sensing structures, and gives higher reliability and sensitivity than relying on changes in the conductance of the DNA strands themselves. The basic components of these sensors are nanoparticles functionalized with biological markers (DNA or protein) for bio-warfare agents as well as nanoelectronic systems for signal transduction. Methodologies were developed in our laboratories to fabricate tools for patterning proteins and DNA structures using custom fabricated cantilever arrays by the industrial partner Nanolnk using a single feedback system. Patterning of nanostructures was achieved through the use of custom pens and inkwell systems. Nanoparticle based screening methods for multiplexed DNA assays were developed by the industrial partner Nanosphere and a multiplexed assay for six select agents was demonstrated via micro array as well as the novel bio-barcode assays. Antibody sandwich assays using DPN template patterning were demonstrated using metal mediated coordination chemistry.