Abstract: Disclosed are thin inorganic membranes having a defined topography that includes pores having a defined diameter of nanometer and sub-nanometer diameter. The thin membranes are resistant to protein denaturing agents, and may be employed in analytical and clinical methods for identifying single amino acid residues within the sequence of a protein, and the pores are other than MspA pores. Methods for making a thin inorganic membrane with nanopore and sub-nanopore topography and conical cone structure are also disclosed. The thin inorganic membrane may be comprised of any denaturant-resistant materials, such as silicon nitride. A method for manufacturing the thin inorganic membrane with nanopores is also provided, and provides a thin surface with a defined conical topography, the nanopores being provided on the membrane surface with an electron beam sputtering technique.

Abstract: Methods of trapping a deformed portion of a double-stranded polynucleotide in a membrane nanopassage are provided. In an aspect, the membrane has a nanopassage that defines a confine region, wherein the membrane separates a first fluid compartment from a second fluid compartment, and the nanopassage is in fluid communication with the first and second compartments. A polynucleotide is provided to the first fluid compartment and optionally a threshold voltage for the membrane and the polynucleotide is determined. A driving voltage across the membrane that is greater than the threshold voltage is applied to force a portion of the polynucleotide sequence into the nanopassage confine region, and decreased to a holding voltage bias to trap the polynucleotide portion in the nanopassage confine region. In particular, at least one nucleotide base-pair is fixably positioned in the nanopassage confine volume. In further embodiments, any of the trapping methods are used to characterize or sequence double stranded DNA.

Abstract: A system that incorporates teachings of the present disclosure may include, for example, a solid-state selector having a vessel for carrying a liquid medium with one or more molecules surrounded by ions, a solid state conductive structure doped with impurities having one or more through-holes extending between two surfaces of the solid state conductive structure positioned within the liquid medium of the vessel, a voltage source coupled to the solid state conductive structure to selectively stimulate the ions surrounding the one or more molecules to pass through the one or more through-holes. Additional embodiments are disclosed.

Abstract: Provided are methods for detecting, characterizing or separating DNA based on methylation. Heterogeneous DNA populations are separated based on DNA methylation by providing a membrane having a nanopore through which an electric field is applied. DNA of interest is introduced, and for a given threshold voltage across the nanopore, only DNA having a methylation parameter of interest may transit the pore, thereby facilitating detection, characterization, or separation of DNA based on methylation. The methods are optionally used to detect a disease state that is associated with DNA methylation including, but not limited to, cancer.

Abstract: A system that incorporates teachings of the present disclosure may include, for example, a solid-state selector having a vessel for carrying a liquid medium with one or more molecules surrounded by ions, a solid state conductive structure doped with impurities having one or more through-holes extending between two surfaces of the solid state conductive structure positioned within the liquid medium of the vessel, a voltage source coupled to the solid state conductive structure to selectively stimulate the ions surrounding the one or more molecules to pass through the one or more through-holes. Additional embodiments are disclosed.

Abstract: A system that incorporates teachings of the present disclosure may include, for example, a solid-state selector having a vessel for carrying a liquid medium with one or more molecules surrounded by ions, a solid state conductive structure doped with impurities having one or more through-holes extending between two surfaces of the solid state conductive structure positioned within the liquid medium of the vessel, a voltage source coupled to the solid state conductive structure to selectively stimulate the ions surrounding the one or more molecules to pass through the one or more through-holes. Additional embodiments are disclosed.

Abstract: Provided are methods for detecting, characterizing or separating DNA based on methylation. Heterogeneous DNA populations are separated based on DNA methylation by providing a membrane having a nanopore through which an electric field is applied. DNA of interest is introduced, and for a given threshold voltage across the nanopore, only DNA having a methylation parameter of interest may transit the pore, thereby facilitating detection, characterization, or separation of DNA based on methylation. The methods are optionally used to detect a disease state that is associated with DNA methylation including, but not limited to, cancer.

Abstract: Methods of trapping a deformed portion of a double-stranded polynucleotide in a membrane nanopassage are provided. In an aspect, the membrane has a nanopassage that defines a confine region, wherein the membrane separates a first fluid compartment from a second fluid compartment, and the nanopassage is in fluid communication with the first and second compartments. A polynucleotide is provided to the first fluid compartment and optionally a threshold voltage for the membrane and the polynucleotide is determined. A driving voltage across the membrane that is greater than the threshold voltage is applied to force a portion of the polynucleotide sequence into the nanopassage confine region, and decreased to a holding voltage bias to trap the polynucleotide portion in the nanopassage confine region. In particular, at least one nucleotide base-pair is fixably positioned in the nanopassage confine volume. In further embodiments, any of the trapping methods are used to characterize or sequence double stranded DNA.

Abstract: A system that incorporates teachings of the present disclosure may include, for example, a solid-state selector having a vessel for carrying a liquid medium with one or more molecules surrounded by ions, a solid state conductive structure doped with impurities having one or more through-holes extending between two surfaces of the solid state conductive structure positioned within the liquid medium of the vessel, a voltage source coupled to the solid state conductive structure to selectively stimulate the ions surrounding the one or more molecules to pass through the one or more through-holes. Additional embodiments are disclosed.