Nanodevices for Single Molecule Studies

Abstract

During the last two decades, biotechnology research has resulted in progress in fields as diverse as the life sciences, agriculture and healthcare. While existing technology enables the analysis of a variety of biological systems, new tools are needed for increasing the efficiency of current methods, and for developing new ones altogether. Interest has grown in single molecule analysis for these reasons. The ability to detect single molecules provides a number of advantages in biomolecular analysis [1–10]. One benefit is an increase of quantification accuracy, as analysis occurs at the ultimate resolution limit. Single molecule techniques also consume less reagent than conventional techniques, and reduce analysis times. Mass production of micro-total-analysis-systems with the ability to analyze single molecules could increase the scope of otherwise prohibitively expensive and protracted processes, such as genomic sequencing and drug discovery. In addition to increasing the efficiency of existing technologies, single molecule analysis grants access to information that is otherwise unobtainable. The characteristics of biomolecular reactions are of interest in this regard. Molecular biologists have used conventional methods to study the ensemble characteristics of many systems. While this approach yields important information regarding the average behavior of a system, it tells little about the specific behavior of single molecules. This includes the time evolution and statistical distribution of parameters obscured by traditional techniques. A variety of nanofabricated structures have emerged as potential tools for single molecule analysis. Several nanostructures have been developed for enhanced optical detection, including quantum dots [11–13], metallic nanobarcodes [14], and nanometric slits [15]. Two optical structures in particular have demonstrated their utility for single molecule analysis – fluidic channels with submicrometer and nanometer dimensions, and optical nanostructures known as zero mode waveguides. Fluidic channels provide controlled transport of analytes through a subfemtoliter focal volume, while zero mode waveguides have