Micro and nanofluidic structures for cell sorting and genomic analysis

• Main Author: Morton, Keith J
• Format: Dissertation
• Language: English
• Published: ProQuest Dissertations & Theses 01-01-2008
• Subjects: Biophysics; Electrical engineering; Plasma physics
• ISBN: 9780549770893; 0549770895

Microfluidic systems promise rapid analysis of small samples in a compact and inexpensive format. But direct scaling of lab bench protocols on-chip is challenging because laminar flows in typical microfluidic devices are characterized by non-mixing streamlines. Common microfluidic mixers and sorters work by diffusion, limiting application to objects that diffuse slowly such as cells and DNA. Recently Huang et.al. developed a passive microfluidic element to continuously separate bio-particles deterministically. In Deterministic Lateral Displacement (DLD), objects are sorted by size as they transit an asymmetric array of microfabricated posts. This thesis further develops DLD arrays with applications in three broad new areas. First the arrays are used, not simply to sort particles, but to move streams of cells through functional flows for chemical treatment—such as on-chip immunofluorescent labeling of blood cells with washing, and on-chip E.coli cell lysis with simultaneous chromosome extraction. Secondly, modular tiling of the basic DLD element is used to construct complex particle handling modes that include beam steering for jets of cells and beads. Thirdly, nanostructured DLD arrays are built using Nanoimprint Lithography (NIL) and continuous-flow separation of 100 nm and 200 nm size particles is demonstrated. Finally a number of ancillary nanofabrication techniques were developed in support of these overall goals, including methods to interface nanofluidic structures with standard microfluidic components such as inlet channels and reservoirs, precision etching of ultra-high aspect ratio (>50:1) silicon nanostructures, and fabrication of narrow (∼ 35 nm) channels used to stretch genomic length DNA.