Nanobiology: Halting steps into a portion of Richard Feynman's vision

The advancement of nanotechnology has slightly opened the door for significant applications in biology. These technologies offer the potential to analyze and manipulate biological systems on the single cell and single molecule scales. The ability to analyze biological systems on these scales provides a direct means to reverse engineer multi-cellular organisms by following gene regulation and protein expression from the point of embryo fertilization onward. The need for amplification for standard bulk assays would be eliminated. Significant diagnostic applications would also be possible especially for genetic disorders and viral based diseases. Unfortunately there are still significant hurdles to overcome so that this potential can be realized and the technology can be used in a more robust manner. This thesis describes a significant effort for advancing the state of the nanoscale art. Specifically: the design and development of microfluidic devices for manipulating and analyzing DNA and E. coli cells, and the design and development of a modular DSP based feedback controller for scanned probe microscope (SPM) and nanomanipulator applications. In addition two significant applications of the DSP controller are presented: controlling the Q of an SPM microcantilever and sculpting the force potential of optical tweezers on the nanometer scale. With the microfluidic devices described here single DNA molecules from 2–200 kbp were sized and sorted with equivalent or better resolution than gel electrophoresis methods and in less time. Using similar techniques a disposable fluorescent cell sorter was developed and demonstrated by sorting green fluorescent protein E. coli cells from wild type cells. Using the DSP electronics the Q of an SPM microcantilever was controlled over three orders of magnitude using force feedback techniques. The Q can be lowered to one, enabling high speed tapping mode scanning ten times faster than possible with the natural Q. Using the same basic DSP electronics the potential of optical tweezers was arbitrarily shaped with 10 nm edge resolution.