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978-3-8439-2366-8, Reihe Nanotechnologie
Nanopore-cavity devices for characterization of biological systems
145 Seiten, Dissertation Technische Universität Braunschweig (2015), Softcover, A5
Due to recent increases in drug resistance there has been a rising interest in fast, cheap, and accurate detection of trace molecules, specific DNA or RNA sequences, as well as drug delivery mechanisms, for targeted medication. Here, nanoscaled Coulter-Counter devices have attracted a large amount of attention, but to date have only been successful by using expensive growth and fabrication methods.
During this time advances in “cheap” silicon technology have not been accounted for and in this work we reevaluate this forgotten vista. Here, we show that novel Coulter-Counter devices consisting of a freestanding nanometer thick Si membrane, with a nano-sized channel, can be achieved through the optimization of Inductively Coupled Plasma - Reactive Ion Etch together with selected membrane drilling techniques.
Electrolyte characterization of the resulting devices indicated nanopore diameters in the tens of nanometers, as confirmed by electron microscopy, and the ability to detect particles passing through the nanopore. Furthermore, Atomic Layer Deposited TiO2 was used to decrease the nanopore diameter to single nanometers. This has the additional advantage of decreasing the ionic current dielectric noise component, leading to increased Signal to Noise Ratio and thereby an improved detection limit. Major hurdles for such devices to overcome are their inherent handling complexity due to their brittle membrane and the possibility to make selective array based measurements. Further miniaturization was investigated by replacing one of the electrolyte chambers with a micro-cavity. To this end, a new approach was used by underetching the cavity through the nanopore down to a pre-deposited Ag electrode that was subsequently chlorinated. Here, electrolyte measurements of the final device exhibited the expected linear behavior of a non-polarized “ideal” electrode with respect to both the electrolyte concentration and the applied voltage, allowing for novel measurements like dynamic transport protein flow analysis though controlled loading of the micro-cavity with charged species.
Lastly, we successfully developed and fabricated similar micro-cavity devices with a thin transparent substrate, that would allow for microscope imaging of fluorescent dyes trapped within arrays of micro-cavities. This original approach permits the use of emulsion microscopy without hindrance or contamination risk, thus leaving the front-side free for dynamic evaluation of external stimuli effects on the now freely exposed transport proteins. These results show that silicon may yet have a role to play in highly specialized yet affordable devices, for biomolecular detection and characterization in medicine.