Single Molecule Electrophoresis and Optical Detection Using Thermoplastic Nanofluidic Devices: An Experimental and Simulation Study

Nanofludic devices provide a great platform for single molecular analysis. The unique phenomena in nanoscale gained such interest in investigating the single molecular behavior in nanochannels. Sizes less than 200 nm in one or two-dimensional structures have lead to fascinating observations not accessible in microscale. When a single molecule translocates through a nanotube it interacts with channel walls by adsorption/ desorption, van der Waals interactions and hydrophilic interactions providing a mechanism for separation without any extra additives. Moreover, double layer thickness governed by the background electrolyte plays a vital role. We report single molecular electrophoresis phenomena in nanochannels and nanoslits based on experiment and simulation studies. This will provide the guidance for sequencing DNA by clipped single monomer nucleotides based on their unique time-of-flight (ToF) signatures when electrokinetically driven through a nanotube. The nanofluidic devices were fabricated in thermoplastic devices using mixed micro-scale and nanoscale methodologies. We also report a novel bonding methodology at low temperature using thermoplastic devices with high glass transition substrate sealed to a low glass transition cover plate. This approach prevents distorted nanochannels specially when fabricating nanochannels less than 50 nm to facilitate DNA stretching studies. Genomic mapping of single molecules has gained attention significantly during the last decade. Genomic mapping of DNA molecules facilitated region-specific drug development. We study the development of a nanofluidic-based sensor to monitor chemotherapy responses in cancer patients by stretching their genomic DNA in nanochannels and identifying the specific damage sites