Enhancing the temporal and spatial resolution of solid-state nanopore single-molecule sensors

Thesis (Ph.D.)--Boston UniversitySince the first report of single-molecule detection using the biological nanopore alpha-hemolysin in 1996, nanopores have grown substantially more versatile. The genetic and chemical modification of biological nanopores and the fabrication of synthetic nanopores in solid-state membranes have enabled detection of analytes ranging in size from single nucleotides to large protein complexes. Among the most promising applications of nanopores is single-molecule sequencing, which has the potential to become a routine part of medical care, is compatible with long read lengths, and can detect epigenetically modified bases. Yet in order to further develop nanopores as useful tools for basic research as well as commercial applications, their temporal and spatial limitations must be addressed. Free electrophoretic threading of nucleic acids through a nanopore allows for discrimination based on large features (e.g., molecular length), but is too fast to resolve smaller features (e.g., single nucleotide identity). The first aim of this research is to enhance the temporal resolution of nanopores by tuning their electrostatic interaction with translocating molecules via chemical modification of the nanopore surface. To this end, we designed and fabricated pH-sensitive chemically coated nanopores to slow the translocation of DNA molecules. A practical nanopore sensing device relies on taking measurements from many pores in parallel to provide sufficient robustness (through redundancy) and throughput. Optical detection facilitates parallel throughput, but requires coupling between an analyte feature and a fluorescence source. The second aim is to enhance nanopore spatial resolution via optical detection of chemically activated fluorescence signals associated with single nanopores under total internal reflection (TIR) illumination. We performed numerical simulations of the concentration field of donor molecules near a nanopore and showed that nanopores are theoretically capable of discriminating between features separated by ~ 1 nm or less, a distance that far exceeds the resolution offered by TIR illumination. Finally, we use fluorescence signals to detect unlabeled DNA translocation through spatially addressed nanopores. With this aim we experimentally validate our theoretical predictions and demonstrate a novel highly parallel near-field chemo-optical detection scheme

A tale of two studies: Syntheses of silicon nitride chemical vapor deposition precursors and divalent lanthanide N,N-dimethylaminodiboranate complexes

Silicon nitride thin films have key industrial applications in the manufacturing of semiconductors, but these applications impose strict requirements on the film growth process. Specifically, the SiN films must be deposited at temperatures below 400 °C to avoid device degradation, and they must be deposited conformally to meet the demand of smaller feature sizes. In chapter 1, the synthesis and deposition of a new precursor for silicon nitride thin films, 1,1-diazido-1-silacyclopent-3-ene (1) is described. Precursor 1, a known compound, was synthesized by treating 1,1-dichloro-1-silacyclopent-3-ene with two equivalents of NaN3 in acetonitrile, and was purified by distillation under reduced pressures. Deposition experiments were performed in a hot-wall chemical vapor deposition (CVD) reactor show that 1 deposits films at temperatures as low as 400 °C and with excellent conformality in trenches with aspect ratios up to 3.5:1. Elemental characterization of these films, performed by Auger spectroscopy, show that these films contain Si (~10 %) and N (~10 %) in a 1:1 ratio but have high C (~40 %) and O (~40 %) contents, which is likely attributed to the presence of residual moisture and oxygen in the reaction chamber and the slow removal of volatile organic byproducts. In chapter 2, we describe the syntheses and molecular structures of new SmII and TmII N,N-dimethylaminodiboranate (DMADB) complexes. Treatment of solutions of SmI2(thf)2 in thf with Na(H3BNMe2BH3) results in the formation of Sm(H3BNMe2BH3)2(thf)3 which can be readily converted to the dimethyoxyethane (dme) adduct, Sm(H3BNMe2BH3)2(dme)2 by treatment with dme. We also show that Sm(H3BNMe2BH3)2(thf)3 can be prepared by the reduction of the SmIII compound, Sm(H3BNMe2BH3)3(thf), with KC8,and that addition of 18-crown-6 to this reaction mixture results in the formation of Sm(H3BNMe2BH3)2(18-crown-6). The new TmII complexes were synthesized analogously to 1; treatment of TmI2 solutions in thf with Na(H3BNMe2BH3) resulted in the formation of 1:1 mixtures of Tm(H3BNMe2BH3)2(thf)3 and Tm(H3BNMe2BH3)2(thf)2. IR and 1H NMR data are reported for all these compounds along with their crystal structures