Design And Fabrication Of DNA Molecule Detection Devices Based On Solid-State Nanopores

It is believed that nanopore based detection method is the most potential third generation gene detection technique. To overcome the disadvantages of bio-nanopores, two types of solid-state nanopore devices including SiN nanopore chip and Au nanogap-nanopore chip are designed and manufactured. Meanwhile, simple and low cost silicon nanowire (SiNW) controllable fabrication method is also investigated to support the SiNW-nanogap chip manufacture. Finally, single base molecule is identified after experiments and DNA nanopore translation physical model building. The following novel findings are achieved in this dissertation.1. Silicon nitride (SiN) nanopore chip is manufactured by microelectromechanical systems (MEMS) process with the help of focus ion beam (FIB) and transmission electron microscope (TEM). In our fabrication process, SiN thin film is firstly fabricated with the MEMS process. By the advantages of the wafer level, simple and high yield production from the MEMS fabrication process, a large amount of the SiN film chips are provided for the following nanopore fabrication. FIB is used to thin the SiN film down to 10 nm thick. Then the thinned region is exposed to a high energy electron beam in a high resolution transmission electron microscope operating at 300 KeV to drill a nanopore. The experiments demonstrate that the SiN nanopore chips made by our method are suitable for DNA sequencing.2. Au nanogap-nanoporewas are successfully designed and fabricated by nanoelectromechanical systems (NEMS) technology in this thesis. A pair of Au nanoelectrodes is fabricated by milling an Au nanowire with FIB. At the same time, a nanopore is fabricated through a sandwich structure, where Au nanowire was embedded.3. SiNWs are grown with microscale size and designed position Cu particles as catalyst. Selected area electron diffraction (SAED) and energy dispersive spectroscopy (DES) which equipped on a TEM were used to characterize the nanowire, which demonstrates that the grown nanowiresare amorphous oxygen-poor silicon nanowire and have uniform diameter. The growth mechanism is proposed in our fabrication process. The presence of hydrogenatoms accelerates the formation of Cu silicide and caused more and more silicon dissolution from the Si substrate. Once the dissolved Si atoms in the silicide exceed the supersaturation point, SiNWs will grow from the Cu silicide nucleation sites. The postion, size of SiNWs can be precisely controlled by the position and size of the Cu nanoparticles, thickness of silicon oxide (SiO2) layer and annealing time after carefully designing, which based on the growth mechanism. Therefore, position and size controllable SiNWs are first manufactured with help of micro scale of Cu pattern in the world.4. SiNWs are successfully manufactured in the surface of silicon-silicon oxide-copper (Si-SiO2-Cu) chip in an annealing process in hydrogen and argon atomshpere. Regular-circles of SiNWs are formed when the thickness of Cu film was 200nm. While, unregular morphology of SiNWs is got with 400 nm Cu film. Dewetting traces could be found at the outsided of closed loops. The morphology of SiNWs is quite different when the thickness of Cu film increases to 600 nm. SiNWs networks in which SiNWs connect each other in the surface of substrate can be got during the anneling process. It is experimentally demonstrates that the SiNWs networks have good electrical properties. Our work demonstrates that the in-plane SiNWs can be realized with the simple and controllable method, which provides an efficient and more economic method for nanoeletronic industry to instead the high cost and complex processes of the widely used "top down" approach.5. SiNWs network and loops with controllable shapes are investigated based on our new fabrication process. Regular-circles of SiNWs and array with position, size and numbers that can be actively controlled are manufactured with the help of 200 nm thick Cu pattern (micro size) annealing. SEM results shown that the single circle can be got with Cu patten size between 2.4μm to 4.6 μm. The numbers of circles increases with the size of Cu pattern increasing. And the number has linear relationship with the square of pattern diameter. The diameter of circles which got with big Cu pattern was smaller than 1.6μm and most diameters are below than 1μm. Direction and pattern controlled SiNWs networks can be achieved with 600nm thick Cu pattern fabrication. The smallest critical dimension of SiNWs networks is about 500 nm. Our fabrication method provides a new manufacturing process for nanoscale electrode and nanoelectromechanical devices. Meanwhile, this technology supports the SiNW-nanogap chip manufaction which can be used for DNA sequencing in cheap way.6. Single base molecules and different lengths of DNA molecules detection experiments are carried out. Meanwhile, the DNA nanopore translation physical model is also built to fit experiments dates. Finally, single nucleotide molecules (dATP and dTTP) and short chain DNA molecule (poly (dA) 20 and poly (dT) 20) are identified respectively.