Abstract: Methods and apparatus for long read, label-free, optical nanopore long chain molecule sequencing. In general, the present disclosure describes a novel sequencing technology based on the integration of nanochannels to deliver single long-chain molecules with widely spaced (>wavelength), ˜1-nm aperture “tortuous” nanopores that slow translocation sufficiently to provide massively parallel, single base resolution using optical techniques. A novel, directed self-assembly nanofabrication scheme using simple colloidal nanoparticles is used to form the nanopore arrays atop nanochannels that unfold the long chain molecules. At the surface of the nanoparticle array, strongly localized electromagnetic fields in engineered plasmonic/polaritonic structures allow for single base resolution using optical techniques.

Abstract: Nucleic acid sequencing methods and systems, the systems including nanochannel chip including: a nanochannel formed in an upper surface of the nanochannel chip and; a roof covering the nanochannel and comprising nanopores and a field enhancement structure; and a barrier disposed in the nanochannel. The method including: introducing a buffer solution including long-chain nucleic acids to the nanochannel chip; applying a voltage potential across the nanochannel chip to drive the nucleic acids through the nanochannel, towards the barrier, and to translocate the nucleic acids through nanopores adjacent to the barrier, such that bases of each of the nucleic acids pass through the field enhancement structure one base at a time and emerge onto an upper surface of the roof; detecting the Raman spectra of the bases of the nucleic acids as each base passes through the electromagnetic-field enhancement structure; and sequencing the nucleic acids based on the detected Raman spectra.

Abstract: Nucleic acid sequencing methods and systems, the systems including nanochannel chip including: a nanochannel formed in an upper surface of the nanochannel chip and; a roof covering the nanochannel and comprising nanopores and a field enhancement structure; and a barrier disposed in the nanochannel. The method including: introducing a buffer solution including long-chain nucleic acids to the nanochannel chip; applying a voltage potential across the nanochannel chip to drive the nucleic acids through the nanochannel, towards the barrier, and to translocate the nucleic acids through nanopores adjacent to the barrier, such that bases of each of the nucleic acids pass through the field enhancement structure one base at a time and emerge onto an upper surface of the roof; detecting the Raman spectra of the bases of the nucleic acids as each base passes through the electromagnetic-field enhancement structure; and sequencing the nucleic acids based on the detected Raman spectra.

Abstract: Methods and apparatus for long read, label-free, optical nanopore long chain molecule sequencing. In general, the present disclosure describes a novel sequencing technology based on the integration of nanochannels to deliver single long-chain molecules with widely spaced (>wavelength), ˜1-nm aperture “tortuous” nanopores that slow translocation sufficiently to provide massively parallel, single base resolution using optical techniques. A novel, directed self-assembly nanofabrication scheme using simple colloidal nanoparticles is used to form the nanopore arrays atop nanochannels that unfold the long chain molecules. At the surface of the nanoparticle array, strongly localized electromagnetic fields in engineered plasmonic/polaritonic structures allow for single base resolution using optical techniques.

Abstract: Methods and apparatus for long read, label-free, optical nanopore long chain molecule sequencing. In general, the present disclosure describes a novel sequencing technology based on the integration of nanochannels to deliver single long-chain molecules with widely spaced (>wavelength), ˜1-nm aperture “tortuous” nanopores that slow translocation sufficiently to provide massively parallel, single base resolution using optical techniques. A novel, directed self-assembly nanofabrication scheme using simple colloidal nanoparticles is used to form the nanopore arrays atop nanochannels that unfold the long chain molecules. At the surface of the nanoparticle array, strongly localized electromagnetic fields in engineered plasmonic/polaritonic structures allow for single base resolution using optical techniques.

Abstract: In accordance with the disclosure, a method of forming a nanochannel is provided. The method includes depositing a photosensitive film stack over a substrate; forming a pattern on the film stack using interferometric lithography; depositing a plurality of silica nanoparticles to form a structure over the pattern; removing the pattern while retaining the structure formed by the plurality of silica nanoparticles, wherein the structure comprises one or more enclosed nanochannels, wherein each of the one or more nanochannels comprise one or more sidewalls and a roof; and partially sealing the roof of one or more nanochannels, wherein the roof comprises no more than one unsealed nanochannel per squared micron.

Abstract: Methods and apparatus for long read, label-free, optical nanopore long chain molecule sequencing. In general, the present disclosure describes a novel sequencing technology based on the integration of nanochannels to deliver single long-chain molecules with widely spaced (>wavelength), ˜1-nm aperture “tortuous” nanopores that slow translocation sufficiently to provide massively parallel, single base resolution using optical techniques. A novel, directed self-assembly nanofabrication scheme using simple colloidal nanoparticles is used to form the nanopore arrays atop nanochannels that unfold the long chain molecules. At the surface of the nanoparticle array, strongly localized electromagnetic fields in engineered plasmonic/polaritonic structures allow for single base resolution using optical techniques.

Abstract: Nucleic acid sequencing methods and systems, the systems including nanochannel chip including: a nanochannel formed in an upper surface of the nanochannel chip and; a roof covering the nanochannel and comprising nanopores and a field enhancement structure; and a barrier disposed in the nanochannel. The method including: introducing a buffer solution including long-chain nucleic acids to the nanochannel chip; applying a voltage potential across the nanochannel chip to drive the nucleic acids through the nanochannel, towards the barrier, and to translocate the nucleic acids through nanopores adjacent to the barrier, such that bases of each of the nucleic acids pass through the field enhancement structure one base at a time and emerge onto an upper surface of the roof; detecting the Raman spectra of the bases of the nucleic acids as each base passes through the electromagnetic-field enhancement structure; and sequencing the nucleic acids based on the detected Raman spectra.

Abstract: Methods and apparatus for long read, label-free, optical nanopore long chain molecule sequencing. In general, the present disclosure describes a novel sequencing technology based on the integration of nanochannels to deliver single long-chain molecules with widely spaced (>wavelength), ˜1-nm aperture “tortuous” nanopores that slow translocation sufficiently to provide massively parallel, single base resolution using optical techniques. A novel, directed self-assembly nanofabrication scheme using simple colloidal nanoparticles is used to form the nanopore arrays atop nanochannels that unfold the long chain molecules. At the surface of the nanoparticle array, strongly localized electromagnetic fields in engineered plasmonic/polaritonic structures allow for single base resolution using optical techniques.

Abstract: Methods and apparatus for long read, label-free, optical nanopore long chain molecule sequencing. In general, the present disclosure describes a novel sequencing technology based on the integration of nanochannels to deliver single long-chain molecules with widely spaced (>wavelength), ˜1-nm aperture “tortuous” nanopores that slow translocation sufficiently to provide massively parallel, single base resolution using optical techniques. A novel, directed self-assembly nanofabrication scheme using simple colloidal nanoparticles is used to form the nanopore arrays atop nanochannels that unfold the long chain molecules. At the surface of the nanoparticle array, strongly localized electromagnetic fields in engineered plasmonic/polaritonic structures allow for single base resolution using optical techniques.

Abstract: In accordance with the disclosure, a method of forming a nanochannel is provided. The method includes depositing a photosensitive film stack over a substrate; forming a pattern on the film stack using interferometric lithography; depositing a plurality of silica nanoparticles to form a structure over the pattern; removing the pattern while retaining the structure formed by the plurality of silica nanoparticles, wherein the structure comprises one or more enclosed nanochannels, wherein each of the one or more nanochannels comprise one or more sidewalls and a roof; and partially sealing the roof of one or more nanochannels, wherein the roof comprises no more than one unsealed nanochannel per squared micron.

Abstract: Methods and apparatus for long read, label-free, optical nanopore long chain molecule sequencing. In general, the present disclosure describes a novel sequencing technology based on the integration of nanochannels to deliver single long-chain molecules with widely spaced (>wavelength), ˜1-nm aperture “tortuous” nanopores that slow translocation sufficiently to provide massively parallel, single base resolution using optical techniques. A novel, directed self-assembly nanofabrication scheme using simple colloidal nanoparticles is used to form the nanopore arrays atop nanochannels that unfold the long chain molecules. At the surface of the nanoparticle array, strongly localized electromagnetic fields in engineered plasmonic/polaritonic structures allow for single base resolution using optical techniques.

Abstract: In accordance with the aspects of the present disclosure, a method and apparatus is disclosed for three-dimensional imaging interferometric microscopy (IIM), which can use at least two wavelengths to image a three-dimensional object. The apparatus can include a first, a second, and a third optical system. The first optical system is disposed to provide a substantially coherent illumination to the 3D object, wherein the illumination is characterized by a plurality of wavelengths. The second optical system includes an optical image recording device and one or more additional optical components characterized by a numerical aperture NA. The third optical system provides interferometric reintroduction of a portion of the coherent illumination as a reference beam into the second optical system. An image recording device records each sub-image formed as a result of interference between the illumination that is scattered by the 3D object and the reference beam.

Abstract: Methods and apparatus for long read, label-free, optical nanopore long chain molecule sequencing. In general, the present disclosure describes a novel sequencing technology based on the integration of nanochannels to deliver single long-chain molecules with widely spaced (>wavelength), ˜1-nm aperture “tortuous” nanopores that slow translocation sufficiently to provide massively parallel, single base resolution using optical techniques. A novel, directed self-assembly nanofabrication scheme using simple colloidal nanoparticles is used to form the nanopore arrays atop nanochannels that unfold the long chain molecules. At the surface of the nanoparticle array, strongly localized electromagnetic fields in engineered plasmonic/polaritonic structures allow for single base resolution using optical techniques.

Abstract: In accordance with the aspects of the present disclosure, a method and apparatus is disclosed for three-dimensional imaging interferometric microscopy (IIM), which can use at least two wavelengths to image a three-dimensional object. The apparatus can include a first, a second, and a third optical system. The first optical system is disposed to provide a substantially coherent illumination to the 3D object, wherein the illumination is characterized by a plurality of wavelengths. The second optical system includes an optical image recording device and one or more additional optical components characterized by a numerical aperture NA. The third optical system provides interferometric reintroduction of a portion of the coherent illumination as a reference beam into the second optical system. An image recording device records each sub-image formed as a result of interference between the illumination that is scattered by the 3D object and the reference beam.

Abstract: In accordance with the aspects of the present disclosure, a method and apparatus is disclosed for imaging interferometric microscopy (IIM), which can use an immersion medium to enhance resolution up to a resolution of linear systems resolution limit of ?/4n, where ? is the wavelength in free space and n is the index of refraction of a transmission medium.

Abstract: In accordance with the invention, there is a method of forming a nanochannel including depositing a photosensitive film stack over a substrate and forming a pattern on the film stack using interferometric lithography. The method can further include depositing a plurality of silica nanoparticles to form a structure over the pattern and removing the pattern while retaining the structure formed by the plurality of silica nanoparticles, wherein the structure comprises an enclosed nanochannel.

Abstract: In accordance with the invention, there are imaging interferometric microscopes and methods for imaging interferometric microscopy using structural illumination and evanescent coupling for the extension of imaging interferometric microscopy. Furthermore, there are coherent anti-Stokes Raman (CARS) microscopes and methods for coherent anti-Stokes Raman (CARS) microscopy, wherein imaging interferometric microscopy techniques are applied to get material dependent spectroscopic information.

Abstract: In accordance with the invention, there is a method of forming a nanochannel including depositing a photosensitive film stack over a substrate and forming a pattern on the film stack using interferometric lithography. The method can further include depositing a plurality of silica nanoparticles to form a structure over the pattern and removing the pattern while retaining the structure formed by the plurality of silica nanoparticles, wherein the structure comprises an enclosed nanochannel.

Abstract: In accordance with the aspects of the present disclosure, a method and apparatus is disclosed for imaging interferometric microscopy (IIM), which can use an immersion medium to enhance resolution up to a resolution of linear systems resolution limit of ?/4n, where ? is the wavelength in free space and n is the index of refraction of a transmission medium.